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  • 1. Abrahamson, Alexandra
    et al.
    Andersson, Carin
    Jönsson, Maria E.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Fogelberg, Oscar
    Orberg, Jan
    Brunstrom, Bjorn
    Brandt, Ingvar
    Gill EROD in monitoring of CYP1A inducers in fish - A study in rainbow trout (Oncorhynchus mykiss) caged in Stockholm and Uppsala waters2007Inngår i: Aquatic Toxicology, ISSN 0166-445X, E-ISSN 1879-1514, Vol. 85, nr 1, s. 1-8Artikkel i tidsskrift (Fagfellevurdert)
  • 2. Agerstrand, Marlene
    et al.
    Berg, Cecilia
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Bjorlenius, Berndt
    Breitholtz, Magnus
    Brunström, Björn
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Fick, Jerker
    Gunnarsson, Lina
    Larsson, D. G. Joakim
    Sumpter, John P.
    Tysklind, Mats
    Ruden, Christina
    Improving Environmental Risk Assessment of Human Pharmaceuticals2015Inngår i: Environmental Science and Technology, ISSN 0013-936X, E-ISSN 1520-5851, Vol. 49, nr 9, s. 5336-5345Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    This paper presents 10 recommendations for improving the European Medicines Agency's guidance for environmental risk assessment of human pharmaceutical products. The recommendations are based on up-to-date, available science in combination with experiences from other chemical frameworks such as the REACH-legislation for industrial chemicals. The recommendations concern: expanding the scope of the current guideline; requirements to assess the risk for development of antibiotic resistance; jointly performed assessments; refinement of the test proposal; mixture toxicity assessments on active pharmaceutical ingredients with similar modes of action; use of all available ecotoxicity studies; mandatory reviews; increased transparency; inclusion of emission data from production; and a risk management option. We believe that implementation of our recommendations would strengthen the protection of the environment and be beneficial to society. Legislation and guidance documents need to be updated at regular intervals in order to incorporate new knowledge from the scientific community. This is particularly important for regulatory documents concerning pharmaceuticals in the environment since this is a research field that has been growing substantially in the last decades.

  • 3.
    Andersson, Marie
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Cellular transport and secretion of the cyanobacterial neurotoxin BMAA into milk and egg: Implications for developmental neurotoxicity2015Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The cyanobacterial amino acid β-N-methylamino-L-alanine (BMAA) is a neurotoxin implicated in the etiology of neurodegenerative diseases. Cyanobacteria are cosmopolitan organisms present in various environments. BMAA can cause long-term neurodegenerative alterations in rats exposed during the neonatal period, a period that corresponds to the last trimester and the first few years of life in humans. As BMAA has been reported to be bioaccumulated in the aquatic food chain and detected in mussels, crayfish and fish used for human consumption, the main aim of this thesis has been to investigate the final step in the mammalian food-chain, i.e. the transfer of BMAA into breast milk.

    Autoradiographic imaging and mass spectrometry analysis showed an enantiomer-selective uptake of BMAA and that the neurotoxin was transferred from lactating mice and rat, via the milk, to the brain of the nursed pups. The results show that transport of BMAA may be disproportional to dose. In addition, BMAA was found present both as free amino acid and tightly associated to proteins in rat brains. Surprisingly, however, no association to milk proteins was found. In vitro studies of murine (HC11) and human (MCF7) mammary epithelial cells suggest that BMAA can pass the human mammary epithelium into milk. Additional transport studies on human intestinal, glioblastoma and neuroblastoma cells showed that L-BMAA was consistently favored over D-BMAA and that the transport was mediated by several amino acid transporters. We also demonstrated that egg-laying quail transfer BMAA to its offspring by deposition in the eggs, particularly in the yolk but also in the albumen. Furthermore, comparative analysis of carboxyl- and methyl-labeled [14C]-BMAA suggested that BMAA was not metabolized to a large degree.

    Altogether, the results indicate that BMAA can be transferred from mothers, via the milk, to the brain of nursed human infants. Determinations of BMAA in mothers’ milk and cows’ milk are therefore warranted. We also propose that birds’ eggs could be an additional source of BMAA exposure in humans. It might therefore be of concern that mussels are increasingly used as feed in commercial egg production.

    Delarbeid
    1. Maternal Transfer of the Cyanobacterial Neurotoxin beta-N-Methylamino-L-Alanine (BMAA) via Milk to Suckling Offspring
    Åpne denne publikasjonen i ny fane eller vindu >>Maternal Transfer of the Cyanobacterial Neurotoxin beta-N-Methylamino-L-Alanine (BMAA) via Milk to Suckling Offspring
    Vise andre…
    2013 (engelsk)Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 10, s. e78133-Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    The cyanobacterial neurotoxin beta-N-methylamino-L-alanine (BMAA) has been implicated in the etiology of neurodegenerative disease and proposed to be biomagnified in terrestrial and aquatic food chains. We have previously shown that the neonatal period in rats, which in humans corresponds to the last trimester of pregnancy and the first few years of age, is a particularly sensitive period for exposure to BMAA. The present study aimed to examine the secretion of C-14-labeled L-and D-BMAA into milk in lactating mice and the subsequent transfer of BMAA into the developing brain. The results suggest that secretion into milk is an important elimination pathway of BMAA in lactating mothers and an efficient exposure route predominantly for L-BMAA but also for D-BMAA in suckling mice. Following secretion of [C-14] L-BMAA into milk, the levels of [C-14] L-BMAA in the brains of the suckling neonatal mice significantly exceeded the levels in the maternal brains. In vitro studies using the mouse mammary epithelial HC11 cell line confirmed a more efficient influx and efflux of L-BMAA than of D-BMAA in cells, suggesting enantiomer-selective transport. Competition experiments with other amino acids and a low sodium dependency of the influx suggests that the amino acid transporters LAT1 and LAT2 are involved in the transport of L-BMAA into milk. Given the persistent neurodevelopmental toxicity following injection of L-BMAA to neonatal rodent pups, the current results highlight the need to determine whether BMAA is enriched mother's and cow's milk.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-211448 (URN)10.1371/journal.pone.0078133 (DOI)000326037000089 ()
    Tilgjengelig fra: 2013-11-27 Laget: 2013-11-25 Sist oppdatert: 2017-12-06bibliografisk kontrollert
    2. Transfer of developmental neurotoxin beta-N-methylamino-L-alanine (BMAA) via milk to nursed offspring: Studies by mass spectrometry and image analysis
    Åpne denne publikasjonen i ny fane eller vindu >>Transfer of developmental neurotoxin beta-N-methylamino-L-alanine (BMAA) via milk to nursed offspring: Studies by mass spectrometry and image analysis
    2016 (engelsk)Inngår i: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 258, s. 108-114Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    The cyanobacterial non-proteinogenic amino acid beta-N-methylamino-L-alanine (BMAA) is proposed to be involved in the etiology of amyotrophic lateral sclerosis/parkinsonism dementia complex. When administered as single doses to neonatal rats, BMAA gives rise to cognitive and neurodegenerative impairments in the adult animal. Here, we employed mass spectrometry (LC-MS/MS) and autoradiographic imaging to examine the mother-to-pup transfer of BMAA in rats. The results show that unchanged BMAA was secreted into the milk and distributed to the suckling pups. The concentration of BMAA in pup stomach milk and the neonatal liver peaked after 8 h, while the concentration in the pup brain increased throughout the study period. About 1 and 6% of the BMAA recovered from adult liver and brain were released following hydrolysis, suggesting that this fraction was associated with protein. No association to milk protein was observed. Injection of rat pups with [methyl-C-14]-L-BMAA or [carboxyl-C-14]-L-BMAA resulted in highly similar distribution patterns, indicating no or low metabolic elimination of the methylamino- or carboxyl groups. In conclusion, BMAA is transported as a free amino acid to rat milk and suckling pups. The results strengthen the proposal that mothers' milk could be a source of exposure for BMAA in human infants. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

    Emneord
    BMAA; Cyanobacterial neurotoxin, kinetics; Milk secretion; Developmental neurotoxicity; Mother-to-offspring transfer
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-265847 (URN)10.1016/j.toxlet.2016.06.015 (DOI)000381648300012 ()27320960 (PubMedID)
    Prosjekter
    Milk, secretion, BMAA, beta-N-methylamino-L-alanine, autoradiography, mass spectrometry
    Forskningsfinansiär
    Swedish Research Council Formas
    Tilgjengelig fra: 2015-11-03 Laget: 2015-11-03 Sist oppdatert: 2017-05-12bibliografisk kontrollert
    3. Potential transfer of neurotoxic amino acid beta-N-methylamino-L-alanine (BMAA) from mother to infant during breast-feeding: Predictions from human cell lines
    Åpne denne publikasjonen i ny fane eller vindu >>Potential transfer of neurotoxic amino acid beta-N-methylamino-L-alanine (BMAA) from mother to infant during breast-feeding: Predictions from human cell lines
    2017 (engelsk)Inngår i: Toxicology and Applied Pharmacology, ISSN 0041-008X, E-ISSN 1096-0333, Vol. 320, s. 40-50Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    β-N-methylamino-alanine (BMAA) is a non-protein amino acid produced by cyanobacteria, diatoms and dinoflagellates. BMAA has potential to biomagnify in a terrestrial food chain, and to bioaccumulate in fish and shellfish. We have reported that administration of [14C]l-BMAA to lactating mice and rats results in a mother to off-spring transfer via the milk. A preferential enantiomer-specific uptake of [14C]l-BMAA has also been demonstrated in differentiated murine mammary epithelium HC11 cells. These findings, together with neurotoxic effects of BMAA demonstrated both in vitro and in vivo, highlight the need to determine whether such transfer could also occur in humans. Here, we used four cell lines of human origin to examine and compare the transport of the two BMAA enantiomers in vitro. The uptake patterns of [14C]l- and [14C]d-BMAA in the human mammary MCF7 cell line were in agreement with the results in murine HC11 cells, suggesting a potential secretion of BMAA into human breast milk. The permeability coefficients for both [14C]l- and [14C]d-BMAA over monolayers of human intestinal Caco2 cells supported an efficient absorption from the human intestine. As a final step, transport experiments confirmed that [14C]l-and [14C]d-BMAA can be taken up by human SHSY5Y neuroblastoma cells and even more efficiently by human U343 glioblastoma cells. In competition experiments with various amino acids, the ASCT2 specific inhibitor benzylserine was the most effective inhibitor of [14C]l-BMAA uptake tested here. Altogether, our results suggest that BMAA can be transferred from an exposed mother, via the milk, to the brain of the nursed infant.

    sted, utgiver, år, opplag, sider
    Elsevier, 2017
    Emneord
    BMAA, Cellular transport, Amino acid transporters, Breast milk, Neurodegeneration
    HSV kategori
    Forskningsprogram
    Biologi med inriktning mot ekotoxikologi
    Identifikatorer
    urn:nbn:se:uu:diva-265857 (URN)10.1016/j.taap.2017.02.004 (DOI)000396798200006 ()28174119 (PubMedID)
    Forskningsfinansiär
    Swedish Research Council Formas
    Tilgjengelig fra: 2015-11-03 Laget: 2015-11-03 Sist oppdatert: 2019-12-19bibliografisk kontrollert
    4. Protein association of the neurotoxin and non-protein amino acid BMAA (beta-N-methylamino-L-alanine) in the liver and brain following neonatal administration in rats
    Åpne denne publikasjonen i ny fane eller vindu >>Protein association of the neurotoxin and non-protein amino acid BMAA (beta-N-methylamino-L-alanine) in the liver and brain following neonatal administration in rats
    Vise andre…
    2014 (engelsk)Inngår i: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 226, nr 1, s. 1-5Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    The environmental neurotoxin beta-N-methylamino-L-alanine (BMAA) is not an amino acid that is normally found in proteins. Our previous autoradiographic study of H-3-labeled BMAA in adult mice unexpectedly revealed a tissue distribution similar to that of protein amino acids. The aim of this study was to characterize the distribution of free and protein-bound BMAA in neonatal rat tissues following a short exposure using autoradiographic imaging and ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The autoradiographic imaging of C-14-L-BMAA demonstrated a distinct uptake of radioactivity that was retained following acid extraction in tissues with a high rate of cell turnover and/or protein synthesis. The UHPLC-MS/MS analysis conclusively demonstrated a dose-dependent increase of protein-associated BMAA in neonatal rat tissues. The level of protein-associated BMAA in the liver was more than 10 times higher than that in brain regions not fully protected by the blood-brain barrier which may be due to the higher rate of protein synthesis in the liver. In conclusion, this study demonstrated that BMAA was associated with rat proteins suggesting that BMAA may be mis-incorporated into proteins. However, protein-associated BMAA seemed to be cleared over time, as none of the samples from adult rats had any detectable free or protein-associated BMAA.

    Emneord
    ALS/PDC, Cyanobacteria, Autoradiography, Mass spectrometry, Misincorporation, N-(2-aminoethyl) glycine
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-222718 (URN)10.1016/j.toxlet.2014.01.027 (DOI)000332409000001 ()24472610 (PubMedID)
    Forskningsfinansiär
    Swedish Research Council Formas
    Tilgjengelig fra: 2014-04-17 Laget: 2014-04-14 Sist oppdatert: 2017-06-30bibliografisk kontrollert
    5. Deposition of cyanobacterial neurotoxin beta-N-methylamino-L-alanine (L-BMAA) in birds' egg: A potential source of BMAA exposure in humans
    Åpne denne publikasjonen i ny fane eller vindu >>Deposition of cyanobacterial neurotoxin beta-N-methylamino-L-alanine (L-BMAA) in birds' egg: A potential source of BMAA exposure in humans
    (engelsk)Manuskript (preprint) (Annet vitenskapelig)
    Emneord
    BMAA, beta-N-methylamino-L-alanine, quail, metabolism, autoradiography
    HSV kategori
    Forskningsprogram
    Biologi med inriktning mot ekotoxikologi
    Identifikatorer
    urn:nbn:se:uu:diva-265859 (URN)
    Forskningsfinansiär
    Swedish Research Council Formas
    Tilgjengelig fra: 2015-11-03 Laget: 2015-11-03 Sist oppdatert: 2016-01-13
  • 4.
    Andersson, Marie
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Ersson, Lisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Brandt, Ingvar
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Bergström, Ulrika
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Potential transfer of neurotoxic amino acid beta-N-methylamino-L-alanine (BMAA) from mother to infant during breast-feeding: Predictions from human cell lines2017Inngår i: Toxicology and Applied Pharmacology, ISSN 0041-008X, E-ISSN 1096-0333, Vol. 320, s. 40-50Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    β-N-methylamino-alanine (BMAA) is a non-protein amino acid produced by cyanobacteria, diatoms and dinoflagellates. BMAA has potential to biomagnify in a terrestrial food chain, and to bioaccumulate in fish and shellfish. We have reported that administration of [14C]l-BMAA to lactating mice and rats results in a mother to off-spring transfer via the milk. A preferential enantiomer-specific uptake of [14C]l-BMAA has also been demonstrated in differentiated murine mammary epithelium HC11 cells. These findings, together with neurotoxic effects of BMAA demonstrated both in vitro and in vivo, highlight the need to determine whether such transfer could also occur in humans. Here, we used four cell lines of human origin to examine and compare the transport of the two BMAA enantiomers in vitro. The uptake patterns of [14C]l- and [14C]d-BMAA in the human mammary MCF7 cell line were in agreement with the results in murine HC11 cells, suggesting a potential secretion of BMAA into human breast milk. The permeability coefficients for both [14C]l- and [14C]d-BMAA over monolayers of human intestinal Caco2 cells supported an efficient absorption from the human intestine. As a final step, transport experiments confirmed that [14C]l-and [14C]d-BMAA can be taken up by human SHSY5Y neuroblastoma cells and even more efficiently by human U343 glioblastoma cells. In competition experiments with various amino acids, the ASCT2 specific inhibitor benzylserine was the most effective inhibitor of [14C]l-BMAA uptake tested here. Altogether, our results suggest that BMAA can be transferred from an exposed mother, via the milk, to the brain of the nursed infant.

  • 5.
    Andersson, Marie
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Karlsson, Oskar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap. Karolinska Inst, Dept Clin Neurosci, Ctr Mol Med, SE-17176 Stockholm, Sweden.
    Banack, Sandra
    Inst Ethnomed, POB 3464, Jackson, WY 83001 USA.
    Brandt, Ingvar
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Transfer of developmental neurotoxin beta-N-methylamino-L-alanine (BMAA) via milk to nursed offspring: Studies by mass spectrometry and image analysis2016Inngår i: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 258, s. 108-114Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The cyanobacterial non-proteinogenic amino acid beta-N-methylamino-L-alanine (BMAA) is proposed to be involved in the etiology of amyotrophic lateral sclerosis/parkinsonism dementia complex. When administered as single doses to neonatal rats, BMAA gives rise to cognitive and neurodegenerative impairments in the adult animal. Here, we employed mass spectrometry (LC-MS/MS) and autoradiographic imaging to examine the mother-to-pup transfer of BMAA in rats. The results show that unchanged BMAA was secreted into the milk and distributed to the suckling pups. The concentration of BMAA in pup stomach milk and the neonatal liver peaked after 8 h, while the concentration in the pup brain increased throughout the study period. About 1 and 6% of the BMAA recovered from adult liver and brain were released following hydrolysis, suggesting that this fraction was associated with protein. No association to milk protein was observed. Injection of rat pups with [methyl-C-14]-L-BMAA or [carboxyl-C-14]-L-BMAA resulted in highly similar distribution patterns, indicating no or low metabolic elimination of the methylamino- or carboxyl groups. In conclusion, BMAA is transported as a free amino acid to rat milk and suckling pups. The results strengthen the proposal that mothers' milk could be a source of exposure for BMAA in human infants. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

  • 6.
    Andersson, Marie
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Karlsson, Oskar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Bergström, Ulrika
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Brittebo, Eva B.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Brandt, Ingvar
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Correction: Maternal Transfer of the Cyanobacterial Neurotoxin β-N-Methylamino-L-Alanine (BMAA) via Milk to Suckling Offspring2015Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 10, artikkel-id e78133Artikkel i tidsskrift (Fagfellevurdert)
  • 7.
    Andersson, Marie
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Karlsson, Oskar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Bergström, Ulrika
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Brittebo, Eva B.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Brandt, Ingvar
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Maternal Transfer of the Cyanobacterial Neurotoxin beta-N-Methylamino-L-Alanine (BMAA) via Milk to Suckling Offspring2013Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 10, s. e78133-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The cyanobacterial neurotoxin beta-N-methylamino-L-alanine (BMAA) has been implicated in the etiology of neurodegenerative disease and proposed to be biomagnified in terrestrial and aquatic food chains. We have previously shown that the neonatal period in rats, which in humans corresponds to the last trimester of pregnancy and the first few years of age, is a particularly sensitive period for exposure to BMAA. The present study aimed to examine the secretion of C-14-labeled L-and D-BMAA into milk in lactating mice and the subsequent transfer of BMAA into the developing brain. The results suggest that secretion into milk is an important elimination pathway of BMAA in lactating mothers and an efficient exposure route predominantly for L-BMAA but also for D-BMAA in suckling mice. Following secretion of [C-14] L-BMAA into milk, the levels of [C-14] L-BMAA in the brains of the suckling neonatal mice significantly exceeded the levels in the maternal brains. In vitro studies using the mouse mammary epithelial HC11 cell line confirmed a more efficient influx and efflux of L-BMAA than of D-BMAA in cells, suggesting enantiomer-selective transport. Competition experiments with other amino acids and a low sodium dependency of the influx suggests that the amino acid transporters LAT1 and LAT2 are involved in the transport of L-BMAA into milk. Given the persistent neurodevelopmental toxicity following injection of L-BMAA to neonatal rodent pups, the current results highlight the need to determine whether BMAA is enriched mother's and cow's milk.

  • 8.
    Andersson, Marie
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Karlsson, Oskar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Brandt, Ingvar
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Deposition of cyanobacterial neurotoxin beta-N-methylamino-L-alanine (L-BMAA) in birds' egg: A potential source of BMAA exposure in humansManuskript (preprint) (Annet vitenskapelig)
  • 9.
    Andersson, Marie
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Karlsson, Oskar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Brandt, Ingvar
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    The environmental neurotoxin β-N-methylamino-l-alanine (l-BMAA) is deposited into birds' eggs2018Inngår i: Ecotoxicology and Environmental Safety, ISSN 0147-6513, E-ISSN 1090-2414, Vol. 147, s. 720-724Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    C-carboxyl-labeled BMAA were compared. The results revealed a pronounced incorporation of radioactivity in the eggs, predominantly in the yolk but also in the albumen. Imaging analysis showed that the concentrations of radioactivity in the liver decreased about seven times between the 24h and the 72h time points, while the concentrations in egg yolk remained largely unchanged. At 72h the egg yolk contained about five times the concentration of radioactivity in the liver. Both BMAA preparations gave rise to similar distribution pattern in the bird tissues and in the eggs, indicating metabolic stability of the labeled groups. The demonstrated deposition into eggs warrants studies of BMAAs effects on bird development. Moreover, birds' eggs may be a source of human BMAA exposure, provided that the laying birds are exposed to BMAA via their diet.

  • 10. Bakshi, Mayur V
    et al.
    Barjaktarovic, Zarko
    Azimzadeh, Omid
    Kempf, Stefan J.
    Merl, Juliane
    Hauck, Stefanie M.
    Buratovic, Sonja
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Eriksson, Per
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Atkinson, Michael J.
    Tapio, Soile
    Total body exposure to low-dose ionizing radiation induces long term alterations to the liver proteome of neonatally exposed mice2015Inngår i: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907, Vol. 14, nr 1, s. 366-373Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Tens of thousands of people are being exposed daily toenvironmental low-dose gamma radiation. Epidemiological data indicate thatsuch low radiation doses may negatively affect liver function and result in thedevelopment of liver disease. However, the biological mechanisms behindthese adverse effects are unknown. The aim of this study was to investigateradiation-induced damage in the liver after low radiation doses. Neonatal maleNMRI mice were exposed to total body irradiation on postnatal day 10 usingacute single doses ranging from 0.02 to 1.0 Gy. Early (1 day) and late (7months) changes in the liver proteome were tracked using isotope-codedprotein label technology and quantitative mass spectrometry. Our dataindicate that low and moderate radiation doses induce an immediateinhibition of the glycolysis pathway and pyruvate dehydrogenase availability inthe liver. Furthermore, they lead to significant long-term alterations in lipidmetabolism and increased liver inflammation accompanying inactivation of thetranscription factor peroxisome proliferator-activated receptor alpha. This study contributes to the understanding of the potentialrisk of liver damage in populations environmentally exposed to ionizing radiation.

  • 11. Bakshi, Mayur V.
    et al.
    Barjaktarovic, Zarko
    Azimzadeh, Omid
    Kempf, Stefan J.
    Merl, Juliane
    Hauck, Stefanie M.
    Eriksson, Per
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Buratovic, Sonja
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Atkinson, Michael J.
    Tapio, Soile
    Long-term effects of acute low-dose ionizing radiation on the neonatal mouse heart: a proteomic study2013Inngår i: Radiation and Environmental Biophysics, ISSN 0301-634X, E-ISSN 1432-2099, Vol. 52, nr 4, s. 451-461Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Epidemiological studies establish that children and young adults are especially susceptible to radiation-induced cardiovascular disease (CVD). The biological mechanisms behind the elevated CVD risk following exposure at young age remain unknown. The present study aims to elucidate the long-term effects of ionizing radiation by studying the murine cardiac proteome after exposure to low and moderate radiation doses. NMRI mice received single doses of total body Co-60 gamma-irradiation on postnatal day 10 and were sacrificed 7 months later. Changes in cardiac protein expression were quantified using isotope-coded protein label and tandem mass spectrometry. We identified 32, 31, 66, and 34 significantly deregulated proteins after doses of 0.02, 0.1, 0.5, and 1.0 Gy, respectively. The four doses shared 9 deregulated proteins. Bioinformatics analysis showed that most of the deregulated proteins belonged to a limited set of biological categories, including metabolic processes, inflammatory response, and cytoskeletal structure. The transcription factor peroxisome proliferator-activated receptor alpha was predicted as a common upstream regulator of several deregulated proteins. This study indicates that both adaptive and maladaptive responses to the initial radiation damage persist well into adulthood. It will contribute to the understanding of the long-term consequences of radiation-induced injury and developmental alterations in the neonatal heart.

  • 12. Behrendt, Lars
    et al.
    Jonsson, Maria E.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Goldstone, Jared V.
    Stegeman, John J.
    Induction of cytochrome P450 1 genes and stress response genes in developing zebrafish exposed to ultraviolet radiation2010Inngår i: Aquatic Toxicology, ISSN 0166-445X, E-ISSN 1879-1514, Vol. 98, nr 1, s. 74-82Artikkel i tidsskrift (Fagfellevurdert)
  • 13.
    Beijer, Kristina
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Azoles and Contaminants in Treated Effluents Interact with CYP1 and CYP19 in Fish: 2015Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Numerous contaminants are present in mixtures in the aquatic environment. Among these are the azoles, a group of chemicals that includes both pharmaceuticals and pesticides. Azole fungicides are designed to inhibit lanosterol 14-demethylase (cytochrome P450 (CYP) 51), while other azoles are intended to inhibit aromatase (CYP19), i.e. the enzyme catalyzing biosynthesis of estrogens. In fish, a variety of CYP enzymes are involved in biotransformation of waterborne contaminants, and in metabolism of endogenous compounds including steroidal hormones. The induction of CYP1A protein and 7-ethoxyresorufin O-deethylase (EROD) activity are common biomarkers for exposure to aryl hydrocarbon receptor (AhR) agonists in fish. We developed an assay to measure inhibition of CYP1A activity (EROD) in three-spined stickleback and rainbow trout gill tissue ex vivo. Several azole fungicides were found to be potent inhibitors of CYP1A activity. A wastewater effluent containing high concentrations of pharmaceuticals was also shown to inhibit CYP1A activity. Further, several azoles inhibited CYP19 activity in rainbow trout brain microsomes in vitro. Azole mixtures reduced both CYP1A and CYP19 activity monotonically and in an additive way. Given the additive action of the azoles, studies to determine adverse effects of azole mixtures on CYP-regulated physiological functions in fish are needed. Induction of EROD and of gene expression of CYP1 in several organs was observed in an in vivo exposure with the same effluent shown to inhibit EROD. This finding could imply that there was a mixture of AhR agonists and CYP1A inhibitors in the effluent. Finally, wastewater treatment technologies were evaluated using biomarker responses in rainbow trout exposed to effluents of different treatments. The results from chemical analysis together with the biomarker results show that ozone and granulated active carbon treatment removed most pharmaceuticals, as well as AhR agonists and other chemicals present in the regular effluent. This part of the thesis demonstrates that biomarkers in fish such as induction of CYP1 gene expression are applicable to evaluate the efficiency of different treatment technologies for wastewater.

    Delarbeid
    1. CYP1A inhibition in fish gill filaments: a novel assay applied on pharmaceuticals and other chemicals
    Åpne denne publikasjonen i ny fane eller vindu >>CYP1A inhibition in fish gill filaments: a novel assay applied on pharmaceuticals and other chemicals
    2010 (engelsk)Inngår i: Aquatic Toxicology, ISSN 0166-445X, E-ISSN 1879-1514, Vol. 96, nr 2, s. 145-150Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    The gill filament 7-ethoxyresorufin O-deethylase (EROD) assay was originally developed as a biomarker for cytochrome P4501A (CYP1A) induction by Ah-receptor agonists in water. In this study, the assay was adapted to measure inhibition of CYP1A activity in fish gill filaments ex vivo. The experiments were carried out using gill arch filaments from beta-naphthoflavone (betaNF)-exposed three-spined stickleback (Gasterosteus aculeatus). Candidate CYP1A inhibitors were added to the assay buffer. Nine selected pharmaceuticals and five known or suspected CYP1A-modulating chemicals were examined with regard to their ability to reduce EROD activity in gill filaments. Ellipticine, a well characterized CYP1A inhibitor, was the most effective inhibitor of the compounds tested. At a concentration in the assay buffer of 1 microM the antifungal azoles ketoconazole, miconazole and bitertanol, and the plant flavonoid acacetin reduced gill EROD activity by more than 50%, implying IC50 values below 1 microM. These compounds have previously been shown to inhibit EROD activity in liver microsomes from fish and mammals at similar concentrations. The proton pump inhibitor omeprazole reduced the gill EROD activity by 39% at 10 microM. It is concluded that the modified gill filament EROD assay is useful to screen for waterborne pollutants that inhibit catalytic CYP1A activity in fish gills.

    Emneord
    Gill filament assay, CYP inhibition, Pharmaceuticals, Antifungal azoles, Three-spined stickleback, EROD activity
    HSV kategori
    Forskningsprogram
    Ekotoxikologi
    Identifikatorer
    urn:nbn:se:uu:diva-120904 (URN)10.1016/j.aquatox.2009.10.018 (DOI)000274978500009 ()19913926 (PubMedID)
    Tilgjengelig fra: 2010-03-17 Laget: 2010-03-17 Sist oppdatert: 2018-01-12bibliografisk kontrollert
    2. Azoles additively inhibit cytochrome P450 1 (EROD) and 19 (aromatase) in rainbow trout (Oncorhynchus mykiss)
    Åpne denne publikasjonen i ny fane eller vindu >>Azoles additively inhibit cytochrome P450 1 (EROD) and 19 (aromatase) in rainbow trout (Oncorhynchus mykiss)
    Vise andre…
    2018 (engelsk)Inngår i: Aquatic Toxicology, ISSN 0166-445X, E-ISSN 1879-1514, Vol. 198, s. 73-81Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Antifungal azoles are widely used in medicine, agriculture, and material protection and several antifungal azoles have been found in environmental samples. Although these compounds were designed to inhibit fungal enzymes such as lanosterol-14-demethylase (cytochrome P450 (CYP) 51), it is well established that the inhibitory actions of azoles are not specific for fungal CYP isozymes.

    We refined a gill filament assay to determine the inhibition of CYP1, measured as reduced 7-ethoxyresorufin-O-deethylase (EROD) activity, in rainbow trout (Oncorhynchus mykiss) gill tissue ex vivo. The advantage of this method is that both induction and inhibition of EROD are performed ex vivo. Among thirteen azoles studied, the five that caused the strongest inhibition of gill EROD activity at a concentration of 5 μM were selected for concentration–response assessment. These compounds (bifonazole, clotrimazole, imazalil, miconazole, and prochloraz) showed IC50 values ranging from 0.1 to 1.5 μM. CYP19 (aromatase) inhibition was measured using microsomes from rainbow trout brains. Concentration-response curves for CYP19 inhibition were determined for letrozole, bifonazole, clotrimazole, imazalil, miconazole and prochloraz, which gave IC50 values ranging from 0.02 to 3.3 μM. It was further found that mixtures of the five most potent azoles reduced both CYP1 and 19 catalytic activity in an additive fashion (IC50 = 0.7 μM and 0.6 μM, in the respective assay). Bifonazole (IC50 = 0.1 μM) is not previously known to inhibit CYP1 activity.

    The additive inhibition of CYP1 and CYP19 catalytic activity is an important finding of the present study. We conclude that this additive action of azoles could mediate adverse impacts on CYP regulated physiological functions in environmentally exposed fish.

    Emneord
    Azole fungicide, EROD activity, cytochrome P450 (CYP), CYP1A, CYP19, aromatase, pharmaceutical, contaminant, chemical, fish, rainbow trout, gill, EROD aktivitet, cytokrom P450 (CYP), CYP1A, CYP19, aromatase, läkemedel, azol, fungicid, kemikalier, förorening, fisk, regnbågslax, gäle
    HSV kategori
    Forskningsprogram
    Biologi med inriktning mot miljötoxikologi
    Identifikatorer
    urn:nbn:se:uu:diva-249010 (URN)10.1016/j.aquatox.2018.02.016 (DOI)000430630100008 ()
    Forskningsfinansiär
    Mistra - The Swedish Foundation for Strategic Environmental Research
    Tilgjengelig fra: 2015-04-15 Laget: 2015-04-10 Sist oppdatert: 2018-08-07bibliografisk kontrollert
    3. Effluent from drug manufacturing affects cytochrome P450 1 regulation and function in fish
    Åpne denne publikasjonen i ny fane eller vindu >>Effluent from drug manufacturing affects cytochrome P450 1 regulation and function in fish
    Vise andre…
    2013 (engelsk)Inngår i: Chemosphere, ISSN 0045-6535, E-ISSN 1879-1298, Vol. 90, nr 3, s. 1149-1157Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    We have previously reported very high concentrations of pharmaceuticals in the effluent from a treatment plant receiving wastewater from about 90 bulk drug manufacturers near Hyderabad, India. The main objective of the present study was to examine how high dilutions of this effluent affect mRNA expression of cytochrome P450 (CYP) 1 family genes and ethoxyresorufin O-deethylase (EROD) activity in exposed wildlife, using the three-spined stickleback (Gasterosteus aculeatus) as a model. In gill filaments exposed to diluted effluent ex vivo, EROD activity was strongly inhibited in a concentration-dependent manner. In a subsequent in vivo study, groups of fish were exposed (24. h) to three concentrations of effluent, 0.8%, 1.6% or 3.2%. In this experiment, EROD in gills was induced 27-, 52- or 60-fold, respectively. Accordingly, CYP1A mRNA was markedly up-regulated in gill, liver and brain of fish exposed to all three effluent concentrations. Expression of mRNA for CYP1B1 and CYP1C1 was induced in gills at all concentrations while effects on these genes in liver and brain were weak or absent. The results of a time course study suggested that most CYP1-inducing substances in the effluent were readily metabolised or excreted, because the induced EROD activity and mRNA expression decreased when the fish were transferred to clean water. Considering that CYP1 enzymes play important roles in biotransformation of endogenous and foreign compounds, the observed dual effect of the effluent on CYP1 catalytic activity and mRNA expression suggests that multiple physiological functions could be affected in exposed wildlife.

    Emneord
    CYP1, EROD, Gills, Pharmaceuticals, Three-spined stickleback, Treated wastewater, Drug products, Effluent treatment, Fish, Gene expression, Wastewater treatment, Effluents, cytochrome P450, cytochrome P450 1, cytochrome P450 1A, cytochrome P450 1B1, cytochrome P450 1C1, cytochrome P450 1C2, ethoxyresorufin deethylase, industrial effluent, messenger RNA, tap water, unclassified drug, biotransformation, concentration (composition), drug, ecological modeling, effluent, enzyme activity, manufacturing, metabolism, pollution exposure, teleost, wastewater, water treatment, animal experiment, animal tissue, article, brain, controlled study, enzyme induction, enzyme inhibition, female, Gasterosteus aculeatus, gene, genetic transcription, gill, liver, mortality, nonhuman, spiggin gene, upregulation, vitellogenin gene, waste water treatment plant, Andhra Pradesh, Hyderabad [Andhra Pradesh], India
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-192012 (URN)10.1016/j.chemosphere.2012.09.023 (DOI)000312978700035 ()
    Merknad

    De två första författarna delar förstaförfattarskapet.

    Tilgjengelig fra: 2013-01-24 Laget: 2013-01-15 Sist oppdatert: 2017-12-06bibliografisk kontrollert
    4. Reduction of pharmaceuticals and other contaminants in sewage treatment effluents by active carbon filtration and ozonation: Evaluation using biomarker responses in fish and chemical analysis
    Åpne denne publikasjonen i ny fane eller vindu >>Reduction of pharmaceuticals and other contaminants in sewage treatment effluents by active carbon filtration and ozonation: Evaluation using biomarker responses in fish and chemical analysis
    Vise andre…
    (engelsk)Manuskript (preprint) (Annet vitenskapelig)
    Emneord
    effluent, STP, wastewater, active carbon, ozonation, rainbow trout
    HSV kategori
    Forskningsprogram
    Biologi med inriktning mot ekotoxikologi
    Identifikatorer
    urn:nbn:se:uu:diva-251294 (URN)
    Tilgjengelig fra: 2015-04-15 Laget: 2015-04-15 Sist oppdatert: 2015-07-07
  • 14.
    Beijer, Kristina
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Björlenius, Berndt
    Royal Inst Technol KTH, Albanova Univ Ctr, Sch Biotechnol, SE-10691 Stockholm, Sweden..
    Shaik, Siraz
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi. IUF Leibniz Res Inst Environm Med, Hennekamp 50, D-40225 Dusseldorf, Germany..
    Lindberg, Richard H.
    Umea Univ, Dept Chem, KBC 6A Linnaeus Vag 6, SE-90187 Umea, Sweden..
    Brunström, Björn
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Brandt, Ingvar
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Removal of pharmaceuticals and unspecified contaminants in sewage treatment effluents by activated carbon filtration and ozonation: Evaluation using biomarker responses and chemical analysis2017Inngår i: Chemosphere, ISSN 0045-6535, E-ISSN 1879-1298, Vol. 176, s. 342-351Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Traces of active pharmaceutical ingredients (APIs) and other chemicals are demonstrated in effluents from sewage treatment plants (STPs) and they may affect quality of surface water and eventually drinking water. Treatment of effluents with granular activated carbon (GAC) or ozone to improve removal of APIs and other contaminants was evaluated at two Swedish STPs, Kappala and Uppsala (88 and 103 APIs analyzed). Biomarker responses in rainbow trout exposed to regular and additionally treated effluents were determined. GAC and ozone treatment removed 87-95% of the total concentrations of APIs detected. In Kappala, GAC removed 20 and ozonation (7 g O-3/m(3)) 21 of 24 APIs detected in regular effluent. In Uppsala, GAC removed 25 and ozonation (5.4 g O-3/m(3)) 15 of 25 APIs detected in effluent. GAC and ozonation also reduced biomarker responses caused by unidentified pollutants in STP effluent water. Elevated ethoxyresorufin-O-deethylase (EROD) activity in gills was observed in fish exposed to effluent in both STPs. Gene expression analysis carried out in Kappala showed increased concentrations of cytochrome P450 (CYP1A5 and CYP1C3) transcripts in gills and of CYP1As in liver of fish exposed to effluent. In fish exposed to GAC- or ozone-treated effluent water, gill EROD activity and expression of CYP1As and CYP1C3 in gills and liver were generally equal to or below levels in fish held in tap water. The joint application of chemical analysis and sensitive biomarkers proved useful for evaluating contaminant removal in STPs with new technologies.

  • 15.
    Beijer, Kristina
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Gao, Kai
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Jönsson, Maria E.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Larsson, D. G. J.
    Brunström, Björn
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Brandt, Ingvar
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Effluent from drug manufacturing affects cytochrome P450 1 regulation and function in fish2013Inngår i: Chemosphere, ISSN 0045-6535, E-ISSN 1879-1298, Vol. 90, nr 3, s. 1149-1157Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We have previously reported very high concentrations of pharmaceuticals in the effluent from a treatment plant receiving wastewater from about 90 bulk drug manufacturers near Hyderabad, India. The main objective of the present study was to examine how high dilutions of this effluent affect mRNA expression of cytochrome P450 (CYP) 1 family genes and ethoxyresorufin O-deethylase (EROD) activity in exposed wildlife, using the three-spined stickleback (Gasterosteus aculeatus) as a model. In gill filaments exposed to diluted effluent ex vivo, EROD activity was strongly inhibited in a concentration-dependent manner. In a subsequent in vivo study, groups of fish were exposed (24. h) to three concentrations of effluent, 0.8%, 1.6% or 3.2%. In this experiment, EROD in gills was induced 27-, 52- or 60-fold, respectively. Accordingly, CYP1A mRNA was markedly up-regulated in gill, liver and brain of fish exposed to all three effluent concentrations. Expression of mRNA for CYP1B1 and CYP1C1 was induced in gills at all concentrations while effects on these genes in liver and brain were weak or absent. The results of a time course study suggested that most CYP1-inducing substances in the effluent were readily metabolised or excreted, because the induced EROD activity and mRNA expression decreased when the fish were transferred to clean water. Considering that CYP1 enzymes play important roles in biotransformation of endogenous and foreign compounds, the observed dual effect of the effluent on CYP1 catalytic activity and mRNA expression suggests that multiple physiological functions could be affected in exposed wildlife.

  • 16.
    Beijer, Kristina
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Jönsson, Maria
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Shaik, Siraz
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Behrens, Daphné
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Brunström, Björn
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Brandt, Ingvar
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Azoles additively inhibit cytochrome P450 1 (EROD) and 19 (aromatase) in rainbow trout (Oncorhynchus mykiss)2018Inngår i: Aquatic Toxicology, ISSN 0166-445X, E-ISSN 1879-1514, Vol. 198, s. 73-81Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Antifungal azoles are widely used in medicine, agriculture, and material protection and several antifungal azoles have been found in environmental samples. Although these compounds were designed to inhibit fungal enzymes such as lanosterol-14-demethylase (cytochrome P450 (CYP) 51), it is well established that the inhibitory actions of azoles are not specific for fungal CYP isozymes.

    We refined a gill filament assay to determine the inhibition of CYP1, measured as reduced 7-ethoxyresorufin-O-deethylase (EROD) activity, in rainbow trout (Oncorhynchus mykiss) gill tissue ex vivo. The advantage of this method is that both induction and inhibition of EROD are performed ex vivo. Among thirteen azoles studied, the five that caused the strongest inhibition of gill EROD activity at a concentration of 5 μM were selected for concentration–response assessment. These compounds (bifonazole, clotrimazole, imazalil, miconazole, and prochloraz) showed IC50 values ranging from 0.1 to 1.5 μM. CYP19 (aromatase) inhibition was measured using microsomes from rainbow trout brains. Concentration-response curves for CYP19 inhibition were determined for letrozole, bifonazole, clotrimazole, imazalil, miconazole and prochloraz, which gave IC50 values ranging from 0.02 to 3.3 μM. It was further found that mixtures of the five most potent azoles reduced both CYP1 and 19 catalytic activity in an additive fashion (IC50 = 0.7 μM and 0.6 μM, in the respective assay). Bifonazole (IC50 = 0.1 μM) is not previously known to inhibit CYP1 activity.

    The additive inhibition of CYP1 and CYP19 catalytic activity is an important finding of the present study. We conclude that this additive action of azoles could mediate adverse impacts on CYP regulated physiological functions in environmentally exposed fish.

  • 17.
    Beijer, Kristina
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Lampa, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Nilsson, Peter M.
    SUS Malmo, Dept Clin Sci, Malmo, Sweden..
    Elmstahl, Solve
    Lund Univ, Div Geriatr Med, Dept Hlth Sci, Malmo Univ Hosp, Malmo, Sweden..
    Pedersen, Nancy L.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Interaction between physical activity and television time on blood pressure level: cross-sectional data from 45000 individuals2018Inngår i: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 36, nr 5, s. 1041-1050Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives:The aim was to investigate if there is an interaction between sitting time and leisure time physical activity on blood pressure and if there are age differences and sex differences in this respect.

    Methods:Linear regression analysis on cross-sectional data was performed in more than 45000 men and women from two Swedish cohort studies, EpiHealth (45-75 years) and LifeGene (18-45 years). Self-reported leisure time physical activity was given in five levels from low (level 1) to vigorous physical activity (level 5) and television time was used as a proxy measure of sitting time.

    Results:High physical activity was associated with lower DBP (P=0.001), but not SBP. Active middle-aged men had lower DBP (-1.1mmHg; 95% CI -1.7 to -0.4) compared with inactive participants. Prolonged television time was associated with higher SBP (P<0.001) and DBP (P=0.011) in both sexes and in most age groups. Watching 3h instead of 1h television per day was associated with higher SBP in middle-aged women (SBP: 1.1mmHg; 95% CI 0.7-1.4) and men (SBP: 1.2mmHg; 95% CI 0.8-1.6). Only in young men, a high physical activity (level 4 instead of level 1) could compensate for a prolonged television time (3h per day) in terms of DBP.

    Conclusion:Prolonged television time was associated with higher SBP and DBP in both sexes and at most ages, whereas an increased physical activity was mainly associated with a lower DBP. Only in young men, a high physical activity could compensate for prolonged television time regarding DBP.

  • 18.
    Beijer, kristina
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Shaik, Siraz
    Berndt, Björlenius
    KTH.
    Lindberg, Richard
    Umeå Universitet.
    Brunström, Björn
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Brandt, Ingvar
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Reduction of pharmaceuticals and other contaminants in sewage treatment effluents by active carbon filtration and ozonation: Evaluation using biomarker responses in fish and chemical analysisManuskript (preprint) (Annet vitenskapelig)
  • 19.
    Berg, Cecilia
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Müllerian duct differentiation: a sensitive target for endocrine disrupters in amphibians2013Konferansepaper (Annet vitenskapelig)
  • 20.
    Berg, Cecilia
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Backström, Tobias
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Jämförande fysiologi.
    Winberg, Svante
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Fysiologi.
    Lindberg, Richard
    Brandt, Ingvar
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Developmental Exposure to Fluoxetine Modulates the Serotonin System in Hypothalamus2013Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 1, s. e55053-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The selective serotonin reuptake inhibitor (SSRI) fluoxetine (FLU, Prozac (R)) is commonly prescribed for depression in pregnant women. This results in SSRI exposure of the developing fetus. However, there are knowledge gaps regarding the impact of SSRI exposure during development. Given the role of serotonin in brain development and its cross-talk with sex hormone function, we investigated effects of developmental exposure to pharmacologically relevant concentrations of FLU (3 and 30 nM (measured)) on brain neurotransmitter levels, gonadal differentiation, aromatase activity in brain and gonads, and the thyroid system, using the Xenopus tropicalis model. Tadpoles were chronically exposed (8 weeks) until metamorphosis. At metamorphosis brains were cryosectioned and levels of serotonin, dopamine, norepinephrine, and their metabolites 5-hydroxyindoleacetic acid, 3,4-dihydroxyphenylacetic acid, and homovanillic acid were measured in discrete regions (telencephalon, hypothalamus and the reticular formation) of the cryosections using high-performance liquid chromatography. Exposure to 30 nM FLU increased the concentration of 5-hydroxyindoleacetic acid in hypothalamus compared with controls. FLU exposure did not affect survival, time to metamorphosis, thyroid histology, gonadal sex differentiation, or aromatase activity implying that the effect on the serotonergic neurotransmitter system in the hypothalamus region was specific. The FLU concentration that impacted the serotonin system is lower than the concentration measured in umbilical cord serum, suggesting that the serotonin system of the developing brain is highly sensitive to in utero exposure to FLU. To our knowledge this is the first study showing effects of developmental FLU exposure on brain neurochemistry. Given that SSRIs are present in the aquatic environment the current results warrant further investigation into the neurobehavioral effects of SSRIs in aquatic wildlife.

  • 21.
    Berg, Cecilia
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Lundstedt-Enkel, KatrinUppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.Olovsson, MattsUppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.Persson, SaraSveriges lantbruksuniversitet, Institutionen för kliniska vetenskaper.
    Female Reproduction and Endocrine Disrupting Chemicals (FEMREP 2013)2013Konferanseproceedings (Annet vitenskapelig)
  • 22.
    Berg, Cecilia
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Säfholm, Moa
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Environmental concentrations of norethindrone and progesteroneinhibit egg development in amphibians2013Konferansepaper (Annet vitenskapelig)
  • 23.
    Berg, Cecilia
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Säfholm, Moa
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Reproductive toxicity of progestogens: norethindrone and progesterone inhibit vitellogenesis2013Konferansepaper (Annet vitenskapelig)
  • 24.
    Berg, Cecilia
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Säfholm, Moa
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Jansson, Erika
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Fick, Jerker
    Umeå universitet.
    Brandt, Ingvar
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Effects of Progestin and Estrogen Mixtures: a partial life cycle study on sex differentiation2013Konferansepaper (Annet vitenskapelig)
  • 25. Bergman, Ake
    et al.
    Andersson, Anna-Maria
    Becher, Georg
    van den Berg, Martin
    Blumberg, Bruce
    Bjerregaard, Poul
    Bornehag, Carl-Gustaf
    Bornman, Riana
    Brandt, Ingvar
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Brian, Jayne V.
    Casey, Stephanie C.
    Fowler, Paul A.
    Frouin, Heloise
    Giudice, Linda C.
    Iguchi, Taisen
    Hass, Ulla
    Jobling, Susan
    Juul, Anders
    Kidd, Karen A.
    Kortenkamp, Andreas
    Lind, Monica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Martin, Olwenn V.
    Muir, Derek
    Ochieng, Roseline
    Olea, Nicolas
    Norrgren, Leif
    Ropstad, Erik
    Ross, Peter S.
    Ruden, Christina
    Scheringer, Martin
    Skakkebaek, Niels Erik
    Soder, Olle
    Sonnenschein, Carlos
    Soto, Ana
    Swan, Shanna
    Toppari, Jorma
    Tyler, Charles R.
    Vandenberg, Laura N.
    Vinggaard, Anne Marie
    Wiberg, Karin
    Zoeller, R. Thomas
    Science and policy on endocrine disrupters must not be mixed: a reply to a "common sense" intervention by toxicology journal editors2013Inngår i: Environmental health, ISSN 1476-069X, E-ISSN 1476-069X, Vol. 12, s. 69-Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    The "common sense" intervention by toxicology journal editors regarding proposed European Union endocrine disrupter regulations ignores scientific evidence and well-established principles of chemical risk assessment. In this commentary, endocrine disrupter experts express their concerns about a recently published, and is in our considered opinion inaccurate and factually incorrect, editorial that has appeared in several journals in toxicology. Some of the shortcomings of the editorial are discussed in detail. We call for a better founded scientific debate which may help to overcome a polarisation of views detrimental to reaching a consensus about scientific foundations for endocrine disrupter regulation in the EU.

  • 26. Bergman, Ake
    et al.
    Heindel, Jerrold J.
    Kasten, Tim
    Kidd, Karen A.
    Jobling, Susan
    Neira, Maria
    Zoeller, R. Thomas
    Becher, Georg
    Bjerregaard, Poul
    Bornman, Riana
    Brandt, Ingvar
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Kortenkamp, Andreas
    Muir, Derek
    Drisse, Marie-Noel Brune
    Ochieng, Roseline
    Skakkebaek, Niels E.
    Bylehn, Agneta Sunden
    Iguchi, Taisen
    Toppari, Jorma
    Woodruff, Tracey J.
    The Impact of Endocrine Disruption: A Consensus Statement on the State of the Science2013Inngår i: Journal of Environmental Health Perspectives, ISSN 0091-6765, E-ISSN 1552-9924, Vol. 121, nr 4, s. A104-A106Artikkel i tidsskrift (Annet vitenskapelig)
  • 27.
    Bergman, Åke
    et al.
    Swedish Toxicol Sci Res Ctr Swetox, Sodertalje, Sweden..
    Becher, Georg
    Norwegian Inst Publ Hlth, Oslo, Norway..
    Blumberg, Bruce
    Univ Calif Irvine, Irvine, CA USA..
    Bjerregaard, Poul
    Univ Southern Denmark, Odense, Denmark..
    Bornman, Riana
    Univ Pretoria, Sch Hlth Syst & Publ Hlth, ZA-0002 Pretoria, South Africa..
    Brandt, Ingvar
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Casey, Stephanie C.
    Univ Calif Irvine, Irvine, CA USA..
    Frouin, Heloise
    Vancouver Aquarium Marine Sci Ctr, Vancouver, BC, Canada..
    Giudice, Linda C.
    Univ Calif San Francisco, San Francisco, CA 94143 USA..
    Heindel, Jerrold J.
    Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA..
    Iguchi, Taisen
    Natl Inst Basic Biol, Okazaki, Aichi 444, Japan..
    Jobling, Susan
    Brunel Univ London, Uxbridge, Middx, England..
    Kidd, Karen A.
    Univ New Brunswick, New Brunswick, NJ USA..
    Kortenkamp, Andreas
    Brunel Univ London, Uxbridge, Middx, England..
    Lind, P. Monica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Muir, Derek
    Environm Canada, Burlington, ON L7R 4A6, Canada..
    Ochieng, Roseline
    Aga Khan Univ Hosp, Nairobi, Kenya..
    Ropstad, Erik
    Norwegian Univ Life Sci, Oslo, Norway..
    Ross, Peter S.
    Vancouver Aquarium Marine Sci Ctr, Vancouver, BC, Canada..
    Skakkebaek, Niels Erik
    Univ Copenhagen, Copenhagen Univ Hosp, Copenhagen, Denmark..
    Toppari, Jorma
    Univ Turku, Turku, Finland..
    Vandenberg, Laura N.
    Univ Massachusetts, Amherst, MA 01003 USA..
    Woodruff, Tracey J.
    Univ Calif San Francisco, San Francisco, CA 94143 USA..
    Zoeller, R. Thomas
    Univ Massachusetts, Amherst, MA 01003 USA..
    Manufacturing doubt about endocrine disrupter science - A rebuttal of industry-sponsored critical comments on the UNEP/WHO report "State of the Science of Endocrine Disrupting Chemicals 2012"2015Inngår i: Regulatory toxicology and pharmacology, ISSN 0273-2300, E-ISSN 1096-0295, Vol. 73, nr 3, s. 1007-1017Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    We present a detailed response to the critique of "State of the Science of Endocrine Disrupting Chemicals 2012" (UNEP/WHO, 2013) by financial stakeholders, authored by Lamb et al. (2014). Lamb et al.'s claim that UNEP/WHO (2013) does not provide a balanced perspective on endocrine disruption is based on incomplete and misleading quoting of the report through omission of qualifying statements and inaccurate description of study objectives, results and conclusions. Lamb et al. define extremely narrow standards for synthesizing evidence which are then used to dismiss the UNEP/WHO 2013 report as flawed. We show that Lamb et al. misuse conceptual frameworks for assessing causality, especially the Bradford Hill criteria, by ignoring the fundamental problems that exist with inferring causality from empirical observations. We conclude that Lamb et al.'s attempt of deconstructing the UNEP/WHO (2013) report is not particularly erudite and that their critique is not intended to be convincing to the scientific community, but to confuse the scientific data. Consequently, it promotes misinterpretation of the UNEP/WHO (2013) report by non-specialists, bureaucrats, politicians and other decision makers not intimately familiar with the topic of endocrine disruption and therefore susceptible to false generalizations of bias and subjectivity.

  • 28.
    Bladin, Emelie
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Effects of low-dose developmental exposure to Bisphenol A: Hepatic gene expression and hepatic lipid accumulation in juvenile Fischer 344 rats2015Independent thesis Advanced level (degree of Master (Two Years)), 20 poäng / 30 hpOppgave
    Abstract [en]

    Background: The endocrine-disrupting chemical bisphenol A (BPA) is suggested to have a potential role in the development of obesity and metabolic disorders. Human exposure occurs worldwide and the developmental period seems to be particularly sensitive, even to very low doses. In January 2015 the European Food Safety Authority (EFSA) lowered the tolerable daily intake (TDI) from 50 μg/kg bw/day to 4 μg/kg bw/day. Ingestion of BPA-contaminated food is the main route of exposure and biotransformation occurs in the liver. Little is known about the effects of BPA exposure on basal metabolic rate and hepatic homeostasis.

    Objectives: This study aimed to investigate potential alterations on hepatic gene expression and hepatic lipid accumulation due to low-dose perinatal BPA developmental exposure.

    Methods: Pregnant Fischer 344 rats were exposed to a lower dose (0.5 μg/kg bw/day) and a higher dose (50 μg/kg bw/day) of BPA via their drinking water during gestation and lactation until weaning. The offspring were exposed in utero and during lactation. They were sacrificed at five weeks of age. Liver mRNA gene expression was measured using qPCR and potential lipid accumulation in the liver was examined using image analysis (ImageJ) of micrographs of tissue sections.

    Results: Perinatal exposure to BPA altered the mRNA expression in males. The mRNA levels of the pro adipogenic transcription factor CCAAT/enhancer binding protein, alpha (C/EBP-α), were 26% lower in higher-dose exposed males compared to controls (p=0.05). No significant effects on mRNA expression were seen in females. Liver lipid accumulation was not significantly altered by BPA exposure.

    Conclusion: Perinatal low-dose BPA exposure (0.5 and 50 μg/kg bw/day), altered hepatic expression of one gene involved in adipogenic transcription in the juvenile male offspring. The results support the potential role of low-dose BPA exposure on metabolic homeostasis and it might be of concern with regard to the currently allowed TDI and the ubiquitous exposure among humans

  • 29.
    Bogdanska, Jasna
    et al.
    Stockholm Univ, Dept Biochem & Biophys, SE-10691 Stockholm, Sweden.
    Borg, Daniel
    Swedish Chem Agcy, SE-17267 Stockholm, Sweden.
    Bergström, Ulrika
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Mellring, Maria
    Stockholm Univ, Dept Analyt Chem & Environm Sci, SE-10691 Stockholm, Sweden;Dept Clin Chem, Aleris Medilab, SE-18515 Taby, Sweden.
    Bergman, Ake
    Stockholm Univ, Dept Analyt Chem & Environm Sci, SE-10691 Stockholm, Sweden;Orebro Univ, Sch Sci & Technol, SE-70182 Orebro, Sweden.
    DePierre, Joseph
    Stockholm Univ, Dept Biochem & Biophys, SE-10691 Stockholm, Sweden.
    Nobel, Stefan
    Karolinska Inst, Dept Mol Med & Surg, Sect Integrat Physiol, Biomedicum Quarter 4C,Solnavagen 9, SE-17177 Stockholm, Sweden.
    Tissue distribution of C-14-labelled perfluorooctanoic acid in adult mice after 1-5 days of dietary exposure to an experimental dose or a lower dose that resulted in blood levels similar to those detected in exposed humans2020Inngår i: Chemosphere, ISSN 0045-6535, E-ISSN 1879-1298, Vol. 239, artikkel-id UNSP 124755Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Perfluorooctanoic acid (PFOA), a global environmental pollutant detected in both wildlife and human populations, has several pathophysiological effects in experimental animals, including hepatotoxicity, immunotoxicity, and developmental toxicity. However, details concerning the tissue distribution of PFOA, in particular at levels relevant to humans, are lacking, which limits our understanding of how humans, and other mammals, may be affected by this compound. Therefore, we characterized the tissue distribution of C-14-PFOA in mice in the same manner as we earlier examined its analogues perfluorooctanesulfonate (PFOS) and perfluorobutanesulfonate (PFBS) in order to allow direct comparisons. Following dietary exposure of adult male C57/BL6 mice for 1, 3 or 5 days to a low dose (0.06 mg/kg/day) or a higher experimental dose (22 mg/kg/day) of C-14-PFOA, both scintillation counting and whole-body autoradiography revealed the presence of PFOA in most of the 19 different tissues examined, demonstrating its ability to leave the bloodstream and enter tissues. There were no differences in the pattern of tissue distribution with the low and high dose and the tissue-to-blood ratios were similar. At both doses, PFOA levels were highest in the liver, followed by blood, lungs and kidneys. The body compartments estimated to contain the largest amounts of PFOA were the liver, blood, skin and muscle. In comparison with our identical studies on PFOS and PFBS, PFOA reached considerably higher tissue levels than PFBS, but lower than PFOS. Furthermore, the distribution of PFOA differed notably from that of PFOS, with lower tissue-to-blood ratios in the liver, lungs, kidneys and skin. (C) 2019 Elsevier Ltd. All rights reserved.

  • 30. Bogdanska, Jasna
    et al.
    Sundstrom, Maria
    Bergström, Ulrika
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Borg, Daniel
    Abedi-Valugerdi, Manuchehr
    Bergman, Ake
    DePierre, Joseph
    Nobel, Stefan
    Tissue distribution of S-35-labelled perfluorobutanesulfonic acid in adult mice following dietary exposure for 1-5 days2014Inngår i: Chemosphere, ISSN 0045-6535, E-ISSN 1879-1298, Vol. 98, s. 28-36Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Perfluorobutanesulfonyl fluoride (PBSF) has been introduced as a replacement for its eight-carbon homolog perfluorooctanesulfonyl fluoride (POSF) in the manufacturing of fluorochemicals. Fluorochemicals derived from PBSF may give rise to perfluorobutanesulfonic acid (PFBS) as a terminal degradation product. Although basic mammalian toxicokinetic data exist for PFBS, information on its tissue distribution has only been reported in one study focused on rat liver. Therefore, here we characterized the tissue distribution of PFBS in mice in the same manner as we earlier examined its eight-carbon homolog perfluorooctanesulfonate (PFOS) to allow direct comparisons. Following dietary exposure of adult male C57/BL6 mice for 1,3 or 5 d to 16 mg S-35-PFBS kg(-1) d(-1), both scintillation counting and whole-body autoradiography (WBA) revealed the presence of PFBS in all of the 20 different tissues examined, demonstrating its ability to leave the bloodstream and enter tissues. After 5 d of treatment the highest levels were detected in liver, gastrointestinal tract, blood, kidney, cartilage, whole bone, lungs and thyroid gland. WBA revealed relatively high levels of PFBS in male genital organs as well, with the exception of the testis. The tissue levels increased from 1 to 3 d of exposure but appeared thereafter to level-off in most cases. The estimated major body compartments were whole bone, liver, blood, skin and muscle. This exposure to PFBS resulted in 5-40-fold lower tissue levels than did similar exposure to PFOS, as well as in a different pattern of tissue distribution, including lower levels in liver and lungs relative to blood.

  • 31.
    Buratovic, Sonja
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Low-Dose Ionizing Radiation Induces Neurotoxicity in the Neonate: Acute or fractionated doses and interaction with xenobiotics in mice2016Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    This thesis examines the developmental neurotoxic effects of exposure to low-dose ionizing radiation (IR), alone or together with xenobiotics, during a critical period of neonatal brain development in mice.

    During mammalian brain development there is a period called the brain growth spurt (BGS), which involves extensive growth and maturation of the brain. It is known that neonatal exposure during the BGS to xenobiotics can have a negative impact on neonatal brain development, resulting in impaired cognitive function in the adult mouse. In humans, the BGS starts during the third trimester of pregnancy and continues for approximately 2 years in the child.  

    The present thesis has identified a defined critical period, during the BGS, when IR can induce developmental neurotoxicity in mice. The observed neurotoxicity was not dependent on sex or strain and manifested as altered neurobehaviour in the adult mouse. Furthermore, fractionated dose exposures appear to be as potent as a higher acute dose. The cholinergic system can be a target system for developmental neurotoxicity of IR, since alterations in adult mouse cholinergic system susceptibility were observed. Co-exposure to IR and nicotine exacerbated the behavioural disturbances and cholinergic system dysfunction. Furthermore, co-exposure with the environmental agent paraquat has indicated that the dopaminergic system can be a potential target.  

    In this thesis, clinically relevant doses of IR and a sedative/anesthetic agent (ketamine) were shown to interact and exacerbate defects in adult mouse neurobehaviour, learning and memory, following neonatal exposure, at doses where the single agents did not have any impact on the measured variables. This indicates a shift in the dose-response curve for IR, towards lower doses, if exposure occurs during the neonatal brain development. In addition, co-exposed mice, showing cognitive defects, expressed elevated levels of tau protein in the cerebral cortex. Furthermore, exacerbation of neurochemical deviations were observed following co-exposure compared to irradiation alone.

    Further investigations of neurotoxic effects following fractionated or acute low-dose IR, modelling the clinical situation during repeated CT scans or levels of radiation deposited in non-target tissue during radiotherapy, and possible interaction effects with xenobiotics, is of great importance in the field of radioprotection. 

    Delarbeid
    1. Neonatal exposure to whole body ionizing radiation induces adult neurobehavioural defects: Critical period, dose-response effects and strain and sex comparison
    Åpne denne publikasjonen i ny fane eller vindu >>Neonatal exposure to whole body ionizing radiation induces adult neurobehavioural defects: Critical period, dose-response effects and strain and sex comparison
    Vise andre…
    2016 (engelsk)Inngår i: Behavioural Brain Research, ISSN 0166-4328, E-ISSN 1872-7549, Vol. 304, s. 11-19Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Development of the brain includes periods which can be critical for its normal maturation. The present study investigates specifically vulnerable peri-/postnatal periods in mice which are essential for understanding the etiology behind radiation induced neurotoxicity and functional defects, including evaluation of neurotoxicity between sexes or commonly used laboratory mouse strains following low/moderate doses of ionizing radiation (IR). Male Naval Medical Research Institute (NMRI) mice, whole body irradiated to a single 500 mGy IR dose, on postnatal day (PND) 3 or PND 10 showed an altered adult spontaneous behaviour and impaired habituation capacity, whereas irradiation on PND 19 did not have any impact on the studied variables. Both NMRI and C57bl/6 male and female mice showed an altered adult spontaneous behaviour and impaired habituation following a single whole body irradiation of 500 or 1000 mGy, but not after 20 or 100 mGy, on PND 10. The present study shows that exposure to low/moderate doses of IR during critical life stages might be involved in the induction of neurological/neurodegenerative disorder/disease. A specifically vulnerable period for radiation induced neurotoxicity seems to be around PND 3-10 in mice. Further studies are needed to investigate mechanisms involved in induction of developmental neurotoxicity following low dose irradiation.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-282365 (URN)10.1016/j.bbr.2016.02.008 (DOI)000372939400002 ()26876140 (PubMedID)
    Forskningsfinansiär
    Swedish Radiation Safety AuthorityEU, FP7, Seventh Framework Programme, 29552
    Tilgjengelig fra: 2016-04-05 Laget: 2016-04-05 Sist oppdatert: 2017-11-30bibliografisk kontrollert
    2. Neonatal exposure to a moderate dose of ionizing radiation causes behavioural defects and altered levels of tau protein in mice
    Åpne denne publikasjonen i ny fane eller vindu >>Neonatal exposure to a moderate dose of ionizing radiation causes behavioural defects and altered levels of tau protein in mice
    Vise andre…
    2014 (engelsk)Inngår i: Neurotoxicology, ISSN 0161-813X, E-ISSN 1872-9711, Vol. 45, s. 48-55Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Medical use of ionizing radiation (IR) has great benefits for treatment and diagnostic imaging, butprocedures as computerized tomography (CT) may deliver a significant radiation dose to the patient.Recently, awareness has been raised about possible non-cancer consequences from low dose exposure toIR during critical phases of perinatal and/or neonatal brain development.In the present study neonatal NMRI mice were whole body irradiated with a single dose of gammaradiation (0; 350 and 500 mGy) on postnatal day 10 (PND 10). At 2 and 4 months of age, mice of bothsexes were observed for spontaneous behaviour in a novel home environment. The neuroproteinsCaMKII, GAP-43, synaptophysin and total tau in male mouse cerebral cortex and hippocampus wereanalysed 24 h post-irradiation and in adults at 6 months of age exposed to 0 or 500 mGy on PND 10.A significantly dose-response related deranged spontaneous behaviour in 2- and 4-month-old micewas observed, where both males and females displayed a modified habituation, indicating reducedcognitive function. The dose of 350 mGy seems to be a tentative threshold. Six-month-old male miceshowed a significantly increased level of total tau in cerebral cortex after irradiation to 500 mGy compared to controls. This demonstrates that a single moderate dose of IR, given during a defined criticalperiod of brain development, is sufficient to cause persistently reduced cognitive function. Moreover, anelevation of tau protein was observed in male mice displaying reduced cognitive function.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-240576 (URN)10.1016/j.neuro.2014.09.002 (DOI)000346955100006 ()25265567 (PubMedID)
    Tilgjengelig fra: 2015-01-08 Laget: 2015-01-08 Sist oppdatert: 2017-06-30bibliografisk kontrollert
    3. Developmental effects of fractionated low-dose exposure to gamma radiation on behaviour and susceptibility of the cholinergic system in mice
    Åpne denne publikasjonen i ny fane eller vindu >>Developmental effects of fractionated low-dose exposure to gamma radiation on behaviour and susceptibility of the cholinergic system in mice
    Vise andre…
    2016 (engelsk)Inngår i: International Journal of Radiation Biology, ISSN 0955-3002, E-ISSN 1362-3095, Vol. 92, nr 7, s. 371-379Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Purpose: To investigate whether neonatal exposure to fractionated external gamma radiation and co-exposure to radiation and nicotine can affect/exacerbate developmental neurotoxic effects, including altered behavior/cognitive function and the susceptibility of the cholinergic system in adult male mice. Materials and methods: Neonatal male Naval Medical Research Institute (NMRI) mice were irradiated with one 200 mGy fraction/day and/or exposed to nicotine (66 μg/kg b.w.) twice daily on postnatal day (PND) 10, 10–11, 10–12 or 10–13 (nicotine only). At 2 months of age the animals were tested for spontaneous behavior in a novel home environment, habituation capacity and nicotine-induced behavior. Results: Fractionated irradiation and co-exposure to radiation and nicotine on three consecutive days disrupted behavior and habituation and altered susceptibility of the cholinergic system. All observed effects were significantly more pronounced in mice co-exposed to both radiation and nicotine. Conclusions: The fractionated irradiation regime affects behavior/cognitive function in a similar manner as has previously been observed for single-dose exposures. Neonatal co-exposure to radiation and nicotine, during a critical period of brain development in general and cholinergic system development in particular, enhance these behavioral defects suggesting that the cholinergic system can be a target system for this type of developmental neurotoxic effects.

    Emneord
    Low-dose radiation, nicotine, cholinergic system, cognition, brain development, behavior
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-282366 (URN)10.3109/09553002.2016.1164911 (DOI)000379933800003 ()27043364 (PubMedID)
    Tilgjengelig fra: 2016-04-05 Laget: 2016-04-05 Sist oppdatert: 2017-11-30bibliografisk kontrollert
    4. Developmental effects of neonatal fractionated co-exposure to low-dose gamma radiation and paraquat on behaviour in adult mice
    Åpne denne publikasjonen i ny fane eller vindu >>Developmental effects of neonatal fractionated co-exposure to low-dose gamma radiation and paraquat on behaviour in adult mice
    Vise andre…
    2019 (engelsk)Inngår i: Journal of Applied Toxicology, ISSN 0260-437X, E-ISSN 1099-1263, Vol. 39, nr 4, s. 582-589Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Radiological methods for screening, diagnostics and therapy are often used in healthcare; however, it has recently been reported that developmental exposure to low-dose ionizing radiation (IR) causes neurotoxicity. Environmental chemicals also have the potential to affect the developing brain and the concomitant effects caused by IR and chemicals are of high interest today. We therefore aim to investigate if low-dose IR can interact with the known neurotoxicant paraquat to induce neurotoxicity in the neonatal mouse model. Using the same model, we also aim to investigate if fractionated low-dose IR can be as neurotoxic as higher acute doses. Male mice were exposed to a single dose of paraquat (0.2 or 0.02 mg/kg) on postnatal day 10 and 11. Two hours following paraquat exposure, mice were whole body irradiated with 100 or 300 mGy gamma radiation (Cs-137). Behavioural observations were performed at 2 and 3 months of age. Following behavioural testing, we evaluated striatal dopaminergic gene transcription. Animals co-exposed to IR and paraquat generally displayed altered spontaneous behaviour compared to controls and single agent exposed mice. Stronger effects by combined exposure were also observed on adult memory and learning. However, dopaminergic gene transcript levels remained unchanged by treatment. Co-exposure to low-dose IR and paraquat can interact to exacerbate neurotoxic effects and to impair cognitive function. Furthermore, fractionation of the radiation dose was observed to be as potent as higher acute exposure for induction of developmental neurotoxicity.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-282374 (URN)10.1002/jat.3748 (DOI)000461835200003 ()30426514 (PubMedID)
    Tilgjengelig fra: 2016-04-05 Laget: 2016-04-05 Sist oppdatert: 2019-04-05bibliografisk kontrollert
    5. Ketamine interacts with low dose ionizing radiaiton during brain development to impair cognitive function in mouse
    Åpne denne publikasjonen i ny fane eller vindu >>Ketamine interacts with low dose ionizing radiaiton during brain development to impair cognitive function in mouse
    Vise andre…
    2016 (engelsk)Inngår i: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175Artikkel i tidsskrift (Fagfellevurdert) Submitted
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-282371 (URN)
    Tilgjengelig fra: 2016-04-05 Laget: 2016-04-05 Sist oppdatert: 2017-11-30bibliografisk kontrollert
  • 32.
    Buratovic, Sonja
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Neonatal Exposure to Low-Dose Ionizing Radiation in Mice: Developmental Neurotoxic Effects of Single and Fractionated Doses and Interaction with Nicotine2015Licentiatavhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    This thesis aims to investigate the developmental neurotoxic effects of low-dose exposure to ionizing radiation, alone or together with nicotine, during a defined critical period of neonatal brain development in mice. 

    Investigation of neurotoxic effects following fractionated or acute low-dose radiation, resembling the clinical situation during repeated CT scans or radiation delivered to non-target tissue during radiotherapy, and possible interaction effects with other agents, is of great importance for risk and safety evaluation.

    During mammalian brain development there are defined critical periods for induction of developmental neurotoxic effects. One of these critical periods is called the brain growth spurt (BGS) and involves extensive growth and maturation of the brain. It is known that neonatal exposure during the BGS to low doses of radiation, as well as nicotine, can have a negative impact on neonatal brain development, resulting in impaired cognitive function in the adult mouse. 

    The present studies have shown that developmental neurotoxicity following low-dose irradiation can be induced during the same critical period of brain development as previously has been shown for chemicals. The observed neurotoxicity was manifested as altered spontaneous behaviour and habituation capacity, independent of sex, as well as elevated levels of an Alzheimer-related neuroprotein in the adult mouse. Furthermore, fractionated dose regimes seem to be as potent for induction of neurotoxicity and behavioural disturbances as an equivalent single acute dose. The cholinergic system can be a target system for developmental neurotoxicity of ionizing radiation, either alone or in combination with the cholinergic agent nicotine. Co-exposure to ionizing radiation and nicotine exacerbated the behavioural disturbances and cholinergic system dysfunction observed in these studies.

    Further studies on developmental neurotoxic effects of low-dose neonatal irradiation and interaction with medical drugs and environmental pollutants are important for the field of radioprotection. 

    Delarbeid
    1. Neonatal exposure to a moderate dose of ionizing radiation causes behavioural defects and altered levels of tau protein in mice
    Åpne denne publikasjonen i ny fane eller vindu >>Neonatal exposure to a moderate dose of ionizing radiation causes behavioural defects and altered levels of tau protein in mice
    Vise andre…
    2014 (engelsk)Inngår i: Neurotoxicology, ISSN 0161-813X, E-ISSN 1872-9711, Vol. 45, s. 48-55Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Medical use of ionizing radiation (IR) has great benefits for treatment and diagnostic imaging, butprocedures as computerized tomography (CT) may deliver a significant radiation dose to the patient.Recently, awareness has been raised about possible non-cancer consequences from low dose exposure toIR during critical phases of perinatal and/or neonatal brain development.In the present study neonatal NMRI mice were whole body irradiated with a single dose of gammaradiation (0; 350 and 500 mGy) on postnatal day 10 (PND 10). At 2 and 4 months of age, mice of bothsexes were observed for spontaneous behaviour in a novel home environment. The neuroproteinsCaMKII, GAP-43, synaptophysin and total tau in male mouse cerebral cortex and hippocampus wereanalysed 24 h post-irradiation and in adults at 6 months of age exposed to 0 or 500 mGy on PND 10.A significantly dose-response related deranged spontaneous behaviour in 2- and 4-month-old micewas observed, where both males and females displayed a modified habituation, indicating reducedcognitive function. The dose of 350 mGy seems to be a tentative threshold. Six-month-old male miceshowed a significantly increased level of total tau in cerebral cortex after irradiation to 500 mGy compared to controls. This demonstrates that a single moderate dose of IR, given during a defined criticalperiod of brain development, is sufficient to cause persistently reduced cognitive function. Moreover, anelevation of tau protein was observed in male mice displaying reduced cognitive function.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-240576 (URN)10.1016/j.neuro.2014.09.002 (DOI)000346955100006 ()25265567 (PubMedID)
    Tilgjengelig fra: 2015-01-08 Laget: 2015-01-08 Sist oppdatert: 2017-06-30bibliografisk kontrollert
    2. Effects of fractionated low dose exposure to gamma radiation and the interaction with nicotine on behaviour in mice
    Åpne denne publikasjonen i ny fane eller vindu >>Effects of fractionated low dose exposure to gamma radiation and the interaction with nicotine on behaviour in mice
    Vise andre…
    (engelsk)Manuskript (preprint) (Annet vitenskapelig)
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-242814 (URN)
    Tilgjengelig fra: 2015-02-02 Laget: 2015-02-02 Sist oppdatert: 2015-03-19
  • 33.
    Buratovic, Sonja
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Stenerlöw, Bo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Fredriksson, Anders
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Sundell-Bergman, Synnöve
    Department of Soil and Environment, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Eriksson, Per
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Developmental effects of fractionated low-dose exposure to gamma radiation on behaviour and susceptibility of the cholinergic system in mice2016Inngår i: International Journal of Radiation Biology, ISSN 0955-3002, E-ISSN 1362-3095, Vol. 92, nr 7, s. 371-379Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose: To investigate whether neonatal exposure to fractionated external gamma radiation and co-exposure to radiation and nicotine can affect/exacerbate developmental neurotoxic effects, including altered behavior/cognitive function and the susceptibility of the cholinergic system in adult male mice. Materials and methods: Neonatal male Naval Medical Research Institute (NMRI) mice were irradiated with one 200 mGy fraction/day and/or exposed to nicotine (66 μg/kg b.w.) twice daily on postnatal day (PND) 10, 10–11, 10–12 or 10–13 (nicotine only). At 2 months of age the animals were tested for spontaneous behavior in a novel home environment, habituation capacity and nicotine-induced behavior. Results: Fractionated irradiation and co-exposure to radiation and nicotine on three consecutive days disrupted behavior and habituation and altered susceptibility of the cholinergic system. All observed effects were significantly more pronounced in mice co-exposed to both radiation and nicotine. Conclusions: The fractionated irradiation regime affects behavior/cognitive function in a similar manner as has previously been observed for single-dose exposures. Neonatal co-exposure to radiation and nicotine, during a critical period of brain development in general and cholinergic system development in particular, enhance these behavioral defects suggesting that the cholinergic system can be a target system for this type of developmental neurotoxic effects.

  • 34.
    Buratovic, Sonja
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Stenerlöw, Bo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för biomedicinsk strålningsvetenskap.
    Fredriksson, Anders
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Sundell-Bergman, Synnöve
    Sveriges lantbruksuniversitet, Fakulteten för naturresurser och lantbruksvetenskap, Institutionen för Mark och miljö.
    Eriksson, Per
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Effects of fractionated low dose exposure to gamma radiation and the interaction with nicotine on behaviour in miceManuskript (preprint) (Annet vitenskapelig)
  • 35.
    Buratovic, Sonja
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Stenerlöw, Bo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Fredriksson, Anders
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Sundell-Bergman, Synnöve
    Eriksson, Per
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Low Dose Neonatal Co-exposure to Radiation and Ketamine Negatively Influences Cognition and Alters Neuroprotein Levels in theAdult Mouse2015Konferansepaper (Annet vitenskapelig)
  • 36.
    Buratovic, Sonja
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Stenerlöw, Bo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk strålningsvetenskap.
    Fredriksson, Anders
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Sundell-Bergman, Synnöve
    Sveriges lantbruksuniversitet, Fakulteten för naturresurser och lantbruksvetenskap, Institutionen för Mark och miljö.
    Viberg, Henrik
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Eriksson, Per
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Neonatal exposure to a moderate dose of ionizing radiation causes behavioural defects and altered levels of tau protein in mice2014Inngår i: Neurotoxicology, ISSN 0161-813X, E-ISSN 1872-9711, Vol. 45, s. 48-55Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Medical use of ionizing radiation (IR) has great benefits for treatment and diagnostic imaging, butprocedures as computerized tomography (CT) may deliver a significant radiation dose to the patient.Recently, awareness has been raised about possible non-cancer consequences from low dose exposure toIR during critical phases of perinatal and/or neonatal brain development.In the present study neonatal NMRI mice were whole body irradiated with a single dose of gammaradiation (0; 350 and 500 mGy) on postnatal day 10 (PND 10). At 2 and 4 months of age, mice of bothsexes were observed for spontaneous behaviour in a novel home environment. The neuroproteinsCaMKII, GAP-43, synaptophysin and total tau in male mouse cerebral cortex and hippocampus wereanalysed 24 h post-irradiation and in adults at 6 months of age exposed to 0 or 500 mGy on PND 10.A significantly dose-response related deranged spontaneous behaviour in 2- and 4-month-old micewas observed, where both males and females displayed a modified habituation, indicating reducedcognitive function. The dose of 350 mGy seems to be a tentative threshold. Six-month-old male miceshowed a significantly increased level of total tau in cerebral cortex after irradiation to 500 mGy compared to controls. This demonstrates that a single moderate dose of IR, given during a defined criticalperiod of brain development, is sufficient to cause persistently reduced cognitive function. Moreover, anelevation of tau protein was observed in male mice displaying reduced cognitive function.

  • 37.
    Buratovic, Sonja
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Stenerlöw, Bo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk strålningsvetenskap.
    Sundell-Bergman, S.
    Swedish Univ Agr Sci, Dept Soil & Environm, Umea, Sweden.
    Fredriksson, Anders
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Viberg, Henrik
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Gordh, Torsten
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Eriksson, Per
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Effects on adult cognitive function after neonatal exposure to clinically relevant doses of ionising radiation and ketamine in mice2018Inngår i: British Journal of Anaesthesia, ISSN 0007-0912, E-ISSN 1471-6771, Vol. 120, nr 3, s. 546-554Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Radiological methods for screening, diagnostics and therapy are frequently used in healthcare. In infants and children, anaesthesia/sedation is often used in these situations to relieve the patients' perception of stress or pain. Both ionising radiation (IR) and ketamine have been shown to induce developmental neurotoxic effects and this study aimed to identify the combined effects of these in a murine model. Methods: Male mice were exposed to a single dose of ketamine (7.5 mg kg(-1) body weight) s.c. on postnatal day 10. One hour after ketamine exposure, mice were whole body irradiated with 50-200 mGy gamma radiation (Cs-137). Behavioural observations were performed at 2, 4 and 5 months of age. At 6 months of age, cerebral cortex and hippocampus tissue were analysed for neuroprotein levels. Results: Animals co-exposed to IR and ketamine displayed significant (P <= 0.01) lack of habituation in the spontaneous behaviour test, when compared with controls and single agent exposed mice. In the Morris Water Maze test, co-exposed animals showed significant (P <= 0.05) impaired learning and memory capacity in both the spatial acquisition task and the relearning test compared with controls and single agent exposed mice. Furthermore, in co-exposed mice a significantly (P <= 0.05) elevated level of tau protein in cerebral cortex was observed. Single agent exposure did not cause any significant effects on the investigated endpoints. Conclusion: Co-exposure to IR and ketamine can aggravate developmental neurotoxic effects at doses where the single agent exposure does not impact on the measured variables. These findings show that estimation of risk after paediatric low-dose IR exposure, based upon radiation dose alone, may underestimate the consequences for this vulnerable population.

  • 38.
    Buratovic, Sonja
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Stenerlöw, Bo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Sundell-Bergman, Synnöve
    Eriksson, Per
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Developmental coexposure to gamma-radiation and paraquat can exacerbate cognitive dysfunction in adult mice2015Konferansepaper (Annet vitenskapelig)
  • 39.
    Buratovic, Sonja
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Stenerlöw, Bo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för biomedicinsk strålningsvetenskap.
    Sundell-Bergman, Synnöve
    Sveriges lantbruksuniversitet, Fakulteten för naturresurser och lantbruksvetenskap, Institutionen för Mark och miljö.
    Fredriksson, Anders
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Eriksson, Per
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Coexposure to gamma-radiation and nicotine during a critical period of neonatal brain development can excarebate cognitive defects in adult mice2014Konferansepaper (Fagfellevurdert)
  • 40.
    Buratovic, Sonja
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Stenerlöw, Bo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för biomedicinsk strålningsvetenskap.
    Sundell-Bergman, Synnöve
    Sveriges lantbruksuniversitet, Fakulteten för naturresurser och lantbruksvetenskap, Institutionen för Mark och miljö.
    Fredriksson, Anders
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Eriksson, Per
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Cognitive defects and tau protein alterations in adult mice following neonatal low dose co-exposure to radiation and ketamine2014Konferansepaper (Fagfellevurdert)
  • 41.
    Buratovic, Sonja
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Stenerlöw, Bo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för biomedicinsk strålningsvetenskap.
    Sundell-Bergman, Synnöve
    Sveriges lantbruksuniversitet, Fakulteten för naturresurser och lantbruksvetenskap, Institutionen för Mark och miljö.
    Fredriksson, Anders
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Viberg, Henrik
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Eriksson, Per
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Neonatal exposure to a single low dose of ionising radiation causes persistent disruptions in cognitive abilities and increased levels of tau in mice2013Konferansepaper (Annet vitenskapelig)
    Abstract [en]

    Ionising radiation (IR) is extensively used in the medical field for treatment and diagnostics. Concern has been raised about possible negative consequences from low dose exposure to IR during critical phases of perinatal and/or neonatal brain development. The brain growth spurt, which is characterized by maturation of axonal and dendritic outgrowth, establishment of neural connections and acquisition of new motor and sensory abilities, occurs perinatally in humans and neonatally in mice. By using the neonatal mouse as an animal model we are able to study the effect of IR during early periods of brain development and which consequences it has for the adult animal.

    Neonatal NMRI mice were irradiated (0; 0.35 and 0.5 Gy) at one single occasion on postnatal day 10. At 2- and 4-months of age, spontaneous behaviour was tested in a novel home environment and parameters observed were locomotion, rearing and total activity. Analyses of important neuroproteins in cerebral cortex were performed 24h following irradiation (0 and 0.5 Gy) and at 6-months of age.

    Observations of spontaneous behaviour revealed a significantly deranged behaviour in 2- and 4-month old mice of both sexes irradiated with 0.35 or 0.5 Gy in a dose response related manner. The observed reduced activity during the beginning of the test period and increased activity at the end of the test period indicates a lack of habituation capacity and disrupted cognitive functions. Neuroprotein analyses of cerebral cortex 24h after irradiation and at 6-months of age showed a significantly increased level of tau in mice irradiated with 0.5 Gy compared to controls. This demonstrates that a single dose of IR, given at a defined critical period during brain development, is sufficient to cause persistently reduced cognitive functions and increased levels of tau in mice. 

  • 42.
    Buratovic, Sonja
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Stenerlöw, Bo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Sundell-Bergman, Synnöve
    Fredriksson, Anders
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Viberg, Henrik
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Gordh, Torsten
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Eriksson, Per
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Ketamine interacts with low dose ionizing radiaiton during brain development to impair cognitive function in mouse2016Inngår i: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175Artikkel i tidsskrift (Fagfellevurdert)
  • 43.
    Buratovic, Sonja
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Viberg, Henrik
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Fredriksson, Anders
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Eriksson, Per
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Developmental exposure to the polybrominated diphenyl ether PBDE 209: Neurobehavioural and neuroprotein analysis in adult male and female mice2014Inngår i: Environmental Toxicology and Pharmacology, ISSN 1382-6689, E-ISSN 1872-7077, Vol. 38, nr 2, s. 570-585Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Polybrominated diphenyl ethers (PBDEs), used as flame retardants in polymer products, are reported to cause developmental neurotoxic effects in mammals. The present study have investigated neurotoxic effects arising from neonatal exposure to PBDE 209, including alterations in sex differences, spontaneous behaviour, learning and memory, neuroproteins and altered susceptibility of the cholinergic system in adults. Three-day-old NMRI mice, of both sexes, were exposed to PBDE 209 (2,2',3,3',4,4',5,5',6,6'-decaBDE at 0, 1.4, 6.0 and 14.0 mu mol/kg b.w.). At adult age (2-7 months) a similar developmental neurotoxic effects in both male and female mice were seen, including lack of or reduced habituation to a novel home environment, learning and memory defects, modified response to the cholinergic agent's paraoxon (males) and nicotine (females) indicating increased susceptibility of the cholinergic system. The behavioural defects were dose-response related and persistent. In mice of both sexes and showing behavioural defects, neuroprotein tau was increased. (C) 2014 Elsevier B.V. All rights reserved.

  • 44.
    Buratovic, Sonja
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Viberg, Henrik
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Fredriksson, Anders
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Eriksson, Per
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Developmental exposure to the polybrominated diphenylether PBDE 209: Neurobehavioural and neuroprotein analysis in adult male and female mice2014Inngår i: Environmental Toxicology and Pharmacology, ISSN 1382-6689, E-ISSN 1872-7077, Vol. 38, s. 570-585Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Polybrominated diphenyl ethers (PBDEs), used as flame retardants in polymer products,are reported to cause developmental neurotoxic effects in mammals. The present studyhave investigated neurotoxic effects arising from neonatal exposure to PBDE 209, includingalterations in sex differences, spontaneous behaviour, learning and memory, neuroproteinsand altered susceptibility of the cholinergic system in adults.Three-day-old NMRI mice, of both sexes, were exposed to PBDE 209 (2,2,3,3,4,4,5,5,6,6-decaBDE at 0, 1.4, 6.0 and 14.0 mol/kg b.w.). At adult age (2–7 months) a similardevelopmental neurotoxic effects in both male and female mice were seen, including lackof or reduced habituation to a novel home environment, learning and memory defects,modified response to the cholinergic agent’s paraoxon (males) and nicotine (females) indi-cating increased susceptibility of the cholinergic system. The behavioural defects weredose–response related and persistent. In mice of both sexes and showing behaviouraldefects, neuroprotein tau was increased.

  • 45.
    Castellanos, Cesilie Granum
    et al.
    Department of Production Animal Clinical Sciences, Norwegian School of Veterinary Science, Postboks 8146 Dep, 0033 Oslo, Norway.
    Sorvik, Irene Beate
    Department of Production Animal Clinical Sciences, Norwegian School of Veterinary Science, Postboks 8146 Dep, 0033 Oslo, Norway.; Department of Pharmaceutical Biosciences, University of Oslo, Postboks 1068 Blindern, 0316 Oslo, Norway.
    Tanum, Marte Bruu
    Department of Production Animal Clinical Sciences, Norwegian School of Veterinary Science, Postboks 8146 Dep, 0033 Oslo, Norway.; The Climate and Pollution Agency (Klif), Postboks 8100 Dep, 0032 Oslo, Norway.
    Verhaegen, Steven
    Department of Production Animal Clinical Sciences, Norwegian School of Veterinary Science, Postboks 8146 Dep, 0033 Oslo, Norway.
    Brandt, Ingvar
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Ropstad, Erik
    Department of Production Animal Clinical Sciences, Norwegian School of Veterinary Science, Postboks 8146 Dep, 0033 Oslo, Norway.
    Differential effects of the persistent DDT metabolite methylsulfonyl-DDE in nonstimulated and LH-stimulated neonatal porcine Leydig cells2013Inngår i: Toxicology and Applied Pharmacology, ISSN 0041-008X, E-ISSN 1096-0333, Vol. 267, nr 3, s. 247-255Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    3-Methylsulfonyl-DDE (MeSO2-DDE) is a potent adrenal toxicant formed from the persistent insecticide DDT. MeSO2-DDE is widely present in human plasma, milk and fat, and in tissues of marine mammals. In the present study, we investigated endocrine-disrupting properties of MeSO2-DDE in primary neonatal porcine Leydig cells. Unstimulated and LH-stimulated cells were exposed to MeSO2-DDE at concentrations ranging from 0.6 to 20 mu M for 48 h. Cell viability, hormone secretion and expression of steroidogenesis related genes were recorded. Secretion of testosterone and estradiol was increased in a concentration-dependent fashion in unstimulated Leydig cells, while in LH-stimulated cells, secretion of testosterone, estradiol and progesterone was decreased. The expression of important steroidogenic genes was down-regulated both in unstimulated and LH-stimulated cells. Notably, no significant impairment of cell viability occurred at any exposure except the highest concentration (20 mu M) in LH-stimulated cells. This indicated that the effects on hormone secretion and gene expression were not caused by cytotoxicity. We conclude that the adrenal toxicant MeSO2-DDE disrupts hormone secretion in a complex fashion in neonatal porcine Leydig cells. The different endocrine responses in unstimulated and LH-stimulated cells imply that the endocrine disruptive activity of MeSO2-DDE is determined by the physiological status of the Leydig cells.

  • 46.
    Dhillon, Sundeep S.
    et al.
    Univ Birmingham, Coll Med & Dent Sci, Sch Clin & Expt Med, Birmingham, W Midlands, England.
    Torell, Frida
    Umea Univ, Dept Chem, Computat Life Sci Cluster CLiC, Umea, Sweden;Karlsruhe Inst Technol, Accelerator Lab ACL, Karlsruhe, Germany;AcureOmics, Umea, Sweden.
    Donten, Magdalena
    AcureOmics, Umea, Sweden.
    Lundstedt-Enkel, Katrin
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi. AcureOmics, Umea, Sweden.
    Bennett, Kate
    AcureOmics, Umea, Sweden.
    Raennar, Stefan
    AcureOmics, Umea, Sweden;Sartorius AG, Corp Res, Gottingen, Germany.
    Trygg, Johan
    Umea Univ, Dept Chem, Computat Life Sci Cluster CLiC, Umea, Sweden;Sartorius AG, Corp Res, Gottingen, Germany.
    Lundstedt, Torbjörn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap. AcureOmics, Umea, Sweden.
    Metabolic profiling of zebrafish embryo development from blastula period to early larval stages2019Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 14, nr 5, artikkel-id e0213661Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The zebrafish embryo is a popular model for drug screening, disease modelling and molecular genetics. In this study, samples were obtained from zebrafish at different developmental stages. The stages that were chosen were 3/4, 4/5, 24, 48, 72 and 96 hours post fertilization (hpf). Each sample included fifty embryos. The samples were analysed using gas chromatography time-of-flight mass spectrometry (GC-TOF-MS). Principle component analysis (PCA) was applied to get an overview of the data and orthogonal projection to latent structure discriminant analysis (OPLS-DA) was utilised to discriminate between the developmental stages. In this way, changes in metabolite profiles during vertebrate development could be identified. Using a GC-TOF-MS metabolomics approach it was found that nucleotides and metabolic fuel (glucose) were elevated at early stages of embryogenesis, whereas at later stages amino acids and intermediates in the Krebs cycle were abundant. This agrees with zebrafish developmental biology, as organs such as the liver and pancreas develop at later stages. Thus, metabolomics of zebrafish embryos offers a unique opportunity to investigate large scale changes in metabolic processes during important developmental stages in vertebrate development. In terms of stability of the metabolic profile and viability of the embryos, it was concluded at 72 hpf was a suitable time point for the use of zebrafish as a model system in numerous scientific applications.

  • 47.
    Drakvik, Elina
    et al.
    Karolinska Inst, Inst Environm Med, Nobels Vag 13, SE-17177 Stockholm, Sweden;Stockholm Univ, ACES, SE-10691 Stockholm, Sweden.
    Altenburger, Rolf
    UFZ Helmholtz Ctr Environm Res, Permoserstr 15, D-04318 Leipzig, Germany.
    Aoki, Yasunobu
    Natl Inst Environm Studies, 16-2 Onogawa, Tsukuba, Ibaraki 3058506, Japan.
    Backhaus, Thomas
    Univ Gothenburg, Dept Biol & Environm Sci, Box 461, SE-40530 Gothenburg, Sweden.
    Bahadori, Tina
    US EPA, 1200 Penn Ave NW,MC 8201R, Washington, DC 20460 USA.
    Barouki, Robert
    Univ Paris, Inserm Unit 1124, 45 Rue St Peres, F-75006 Paris, France.
    Brack, Werner
    UFZ Helmholtz Ctr Environm Res, Permoserstr 15, D-04318 Leipzig, Germany;Rhein Westfal TH Aachen, Inst Environm Res, ABBt Aachen Biol, Worringerweg 1, D-52074 Aachen, Germany.
    Cronin, Mark T. D.
    Liverpool John Moores Univ, Sch Pharm & Biomol Sci, Byrom St, Liverpool L3 3AF, Merseyside, England.
    Demeneix, Barbara
    CNRS, MNHN, UMR 7221, 7 Rue Cuvier, F-75005 Paris, France.
    Bennekou, Susanne Hougaard
    Danish Tech Univ, FOOD, Kemitorvet 201, DK-2800 Lyngby, Denmark.
    van Klaveren, Jacob
    Natl Inst Publ Hlth & Environm RIVM, POB 1, NL-3720 BA Bilthoven, Netherlands.
    Kneuer, Carsten
    German Fed Inst Risk Assessment, Pesticide Safety, Max Dohrn Str 8-10, D-10589 Berlin, Germany.
    Kolossa-Gehring, Marike
    German Environm Agcy UBA, Correnspl 1, D-14195 Berlin, Germany.
    Lebret, Erik
    Natl Inst Publ Hlth & Environm RIVM, POB 1, NL-3720 BA Bilthoven, Netherlands;Univ Utrecht, IRAS, Yalelaan 2, NL-3584 CM Utrecht, Netherlands.
    Posthuma, Leo
    Natl Inst Publ Hlth & Environm RIVM, POB 1, NL-3720 BA Bilthoven, Netherlands;Radboud Univ Nijmegen, Dept Environm Sci, Inst Water & Wetland Res, Nijmegen, Netherlands.
    Reiber, Lena
    German Environm Agcy UBA, Correnspl 1, D-14195 Berlin, Germany.
    Rider, Cynthia
    NIEHS, Natl Toxicol Program, 111 TW Alexander Dr,POB 12233,MD K2-12, Res Triangle Pk, NC 27709 USA.
    Ruegg, Joëlle
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi. Karolinska Inst, Inst Environm Med, Nobels Vag 13, SE-17177 Stockholm, Sweden.
    Testa, Giuseppe
    Univ Milan, Dept Oncol, Via S Sofia 9-1, I-20122 Milan, Italy;IEO, Via Adamello 16, I-20139 Milan, Italy.
    van der Burg, Bart
    BioDetect Syst, Sci Pk 406, NL-1098 XH Amsterdam, Netherlands.
    van der Voet, Hilko
    Wageningen Univ & Res, Droevendaalsesteeg 1, NL-6708 PB Wageningen, Netherlands.
    Warhurst, A. Michael
    CHEM Trust, 34b York Way, London N1 9AB, England.
    van de Water, Bob
    Leiden Univ, Leiden Acad Ctr Drug Res, POB 9502, NL-2300 RA Leiden, Netherlands.
    Yamazaki, Kunihiko
    Minist Environm Japan, Chiyoda Ku, 1-2-2 Kasumigaseki, Tokyo 1008975, Japan.
    Oberg, Mattias
    Karolinska Inst, Inst Environm Med, Nobels Vag 13, SE-17177 Stockholm, Sweden.
    Bergman, Ake
    Stockholm Univ, ACES, SE-10691 Stockholm, Sweden;Orebro Univ, Dept Sci & Technol, SE-70182 Orebro, Sweden;Tongji Univ, Coll Environm Sci & Engn, State Key Lab Pollut Control & Resource Reuse, Shanghai 200092, Peoples R China.
    Statement on advancing the assessment of chemical mixtures and their risks for human health and the environment2020Inngår i: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 134, artikkel-id UNSP 105267Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    The number of anthropogenic chemicals, manufactured, by-products, metabolites and abiotically formed transformation products, counts to hundreds of thousands, at present. Thus, humans and wildlife are exposed to complex mixtures, never one chemical at a time and rarely with only one dominating effect. Hence there is an urgent need to develop strategies on how exposure to multiple hazardous chemicals and the combination of their effects can be assessed. A workshop, "Advancing the Assessment of Chemical Mixtures and their Risks for Human Health and the Environment" was organized in May 2018 together with Joint Research Center in Ispra, EUfunded research projects and Commission Services and relevant EU agencies. This forum for researchers and policy-makers was created to discuss and identify gaps in risk assessment and governance of chemical mixtures as well as to discuss state of the art science and future research needs. Based on the presentations and discussions at this workshop we want to bring forward the following Key Messages: We are at a turning point: multiple exposures and their combined effects require better management to protect public health and the environment from hazardous chemical mixtures. Regulatory initiatives should be launched to investigate the opportunities for all relevant regulatory frameworks to include prospective mixture risk assessment and consider combined exposures to (real-life) chemical mixtures to humans and wildlife, across sectors. Precautionary approaches and intermediate measures (e.g. Mixture Assessment Factor) can already be applied, although, definitive mixture risk assessments cannot be routinely conducted due to significant knowledge and data gaps. A European strategy needs to be set, through stakeholder engagement, for the governance of combined exposure to multiple chemicals and mixtures. The strategy would include research aimed at scientific advancement in mechanistic understanding and modelling techniques, as well as research to address regulatory and policy needs. Without such a clear strategy, specific objectives and common priorities, research, and policies to address mixtures will likely remain scattered and insufficient.

  • 48.
    Elmhalli, Fawzeia
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Systematisk biologi.
    Palsson, Katinka
    Royal Inst Technol, Sch Chem Sci & Engn, Dept Chem, Ecol Chem Grp, Stockholm, Sweden.
    Örberg, Jan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Grandi, Giulio
    Swedish Univ Agr Sci SLU, Dept Biomed Sci & Vet Publ Hlth, Uppsala, Sweden.
    Acaricidal properties of ylang-ylang oil and star anise oil against nymphs of Ixodes ricinus (Acari: Ixodidae)2018Inngår i: Experimental & applied acarology, ISSN 0168-8162, E-ISSN 1572-9702, Vol. 76, nr 2, s. 209-220Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Ylang-ylang oil (YYO) from Cananga odorata (Lam.) Hook.f. & Thomson and star anise oil (SAO) from Illicium verum Hook.f. were tested at four concentrations 0.05, 0.1, 0.2, 0.4 mu l/cm(2). Mortality rates were obtained by counting dead nymphs at 30-min intervals during the first 5h after the start of exposure and then at 24, 48 and 72h. Mortality increased with increasing oil concentration and time of exposure. The two highest concentrations of YYO (0.2, 0.4 mu l/cm(2)) gave maximum lethal concentrations (LC) of 50 and 95% mortality after 4.5h exposure. Mortality of 95% was obtained after 24h with the next highest dose (0.1 mu l/cm(2)), whereas LC95 required 3days with the lowest YYO (0.05 mu l/cm(2)). The lethal effect time (LT) was correlated with the duration of exposure, with a significant effect at 0.4l YYO/cm(2) after 3h' (LT50=3.2h, LT95=4.3h). In contrast, only the highest concentration of SAO, 0.4 mu l SAO/cm(2), showed increasing mortality with time of exposure. This reached LT50 after 10h and LT95 after 24h. However, with the lower concentration (0.2 mu l/cm(2)) 50% mortality was reached after 24h and 100% at 72h. At to the lowest concentration of SAO (0.1 mu l/cm(2)), 67% mortality after 48h. The study indicates that YYO and SAO exhibit strong acaricidal properties against nymphs of I. ricinus and suggest that both YYO and SAO should be evaluated as potentially useful in the control of ticks.

  • 49.
    Eriksson, Per
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Buratovic, Sonja
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Fredriksson, Anders
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Stenerlöw, Bo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Sundell-Bergman, Synnöve
    Swedish Univ Agr Sci, Dept Soil & Environm, Uppsala, Sweden.
    Neonatal exposure to whole body ionizing radiation induces adult neurobehavioural defects: Critical period, dose-response effects and strain and sex comparison2016Inngår i: Behavioural Brain Research, ISSN 0166-4328, E-ISSN 1872-7549, Vol. 304, s. 11-19Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Development of the brain includes periods which can be critical for its normal maturation. The present study investigates specifically vulnerable peri-/postnatal periods in mice which are essential for understanding the etiology behind radiation induced neurotoxicity and functional defects, including evaluation of neurotoxicity between sexes or commonly used laboratory mouse strains following low/moderate doses of ionizing radiation (IR). Male Naval Medical Research Institute (NMRI) mice, whole body irradiated to a single 500 mGy IR dose, on postnatal day (PND) 3 or PND 10 showed an altered adult spontaneous behaviour and impaired habituation capacity, whereas irradiation on PND 19 did not have any impact on the studied variables. Both NMRI and C57bl/6 male and female mice showed an altered adult spontaneous behaviour and impaired habituation following a single whole body irradiation of 500 or 1000 mGy, but not after 20 or 100 mGy, on PND 10. The present study shows that exposure to low/moderate doses of IR during critical life stages might be involved in the induction of neurological/neurodegenerative disorder/disease. A specifically vulnerable period for radiation induced neurotoxicity seems to be around PND 3-10 in mice. Further studies are needed to investigate mechanisms involved in induction of developmental neurotoxicity following low dose irradiation.

  • 50.
    Eriksson, Per
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Buratovic, Sonja
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Stenerlöw, Bo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Fredriksson, Anders
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Sundell-Bergman, Synnöve
    Low-dose Ionizing Radiation Interacts with Environmental Agents During Brain Development: Exacerbation of Cognitive Dysfunction inMice2015Konferansepaper (Annet vitenskapelig)
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