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  • 151. Holm, Lena
    et al.
    Blomqvist, Alexandra
    Brandt, Ingvar
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Brunström, Björn
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Ridderstråle, Yvonne
    Berg, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Embryonic exposure to o,p'-DDT causes eggshell thinning and altered shell gland carbonic anhydrase expression in the domestic hen2006In: Environmental Toxicology and Chemistry, ISSN 0730-7268, E-ISSN 1552-8618, Vol. 25, no 10, p. 2787-2793Article in journal (Refereed)
    Abstract [en]

    The mechanism for contaminant-induced eggshell thinning in wild birds remains to be clarified. It is generally assumed, however, that it results from exposure of the adult laying female. We have reported that embryonic exposure to the synthetic estrogen ethynylestradiol (EE2) results in eggshell thinning in the domestic hen. The objective of this study was to investigate whether eggshell thinning can be induced following in ovo exposure to a bioaccumulating estrogenic environmental contaminant, o,p '-DDT. Ethynylestradiol was used as a positive control. Domestic hens exposed in ovo to o,p '-DDT (37 or 75 mu g/g egg) or EE2 (60 ng/g egg) laid eggs with thinner shells than the control birds. The hens from these exposure groups also had a significantly reduced frequency of shell gland capillaries with carbonic anhydrase (CA) activity, a key enzyme in eggshell formation. The decreased number of capillaries with CA activity suggests that a developmentally induced disruption of CA expression in the shell gland was involved in the eggshell thinning found in this study. Egg laying was not affected in hens exposed embryonically to 37 or 75 mu g o,p '-DDT/g egg, whereas it was inhibited in hens exposed to higher doses. Decreased lengths of the left oviduct and its infundibulum were seen after embryonic treatment with o,p '-DDT or EE2. In addition, o,p '-DDT exposure resulted in right oviduct retention. The results support our hypothesis that eggshell thinning in avian wildlife can result from a functional malformation in the shell gland, induced by embryonic exposure to estrogenic substances.

  • 152.
    Isaac, Giorgis
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry. Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Physical and Analytical Chemistry. Analytisk kemi.
    Fredriksson, Anders
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry. Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Danielsson, Rolf
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry. Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Physical and Analytical Chemistry. Analytisk kemi.
    Eriksson, Per
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry. Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Bergquist, Jonas
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry. Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Physical and Analytical Chemistry. Analytisk kemi.
    Brain lipid composition in postnatal iron-induced motor behavior alterations following chronic neuroleptic administration in mice2006In: FEBS Journal, no 273, p. 2232-2243Article in journal (Refereed)
  • 153.
    Jaensson, Alia
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Pheromonal Mediated Behaviour and Endocrine Responses in Salmonids: The impact of Cypermethrin, Copper, and Glyphosate2010Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The effects of cypermethrin, copper and glyphosate on the endocrine system and subsequent response to female pheromones were investigated in mature male brown trout (Salmo trutta) parr.  Responses measured were the amount of strippable milt, blood plasma levels of both an androgen (11-ketotestosterone (11-KT)) and a progestin (17α,20β-dihydroxy-4-pregnen-3-one (17,20b-P)), and behavioural changes. This was done in a two phased investigation where parr were exposed to one of the following via ambient water: 1) 0.1 or 1.0 μg L-1 cypermethrin, 2) 10 or 100 μg L-1 copper (Cu2+), or 3) 150 μg L-1 glyphosate for a 96 hour period.  Phase one was a priming experiment exposing parr to a treatment followed by priming with PGF or ovarian fluid (OVF). Atlantic salmon (Salmo salar) parr were, also exposed to glyphosate during phase I. The second phase was centered on behavioural observations.  Exposed parr were placed in a 35,000 L stream aquarium together with two ovulated females and four anadromous males. After the experiments a blood sample was taken, milt volumes measured and testes weighed.  The plasma was analyzed for 11-KT and 17,20b-P concentrations using radioimmunoassay (RIA).

    Results from phase I-priming: 1.0 μg L-1 cypermethrin exposure lowered 17,20b-P and 11-KT; Copper exposure lowered milt volumes; glyphosate exposure lowered 11-KT in salmon and raised 17,20b-P in trout.  Results from phase II-behaviour: 1.0 μg L-1 cypermethrin exposure lowered 11-KT, milt and spawning behaviour; copper exposure lowered spawning behaviour and raised 11-KT; Glyphosate exposure lowered 11KT; continuous cypermethrin exposure raised 17,20b-P, 11-KT and gave a tendency towards increased aggression. It is concluded that low concentration exposure to the compounds examined can induce negative effects on male salmonid endocrine systems, either through a disruption in the olfactory system or through a direct effect.

    List of papers
    1. Effects of a pyrthroid pesticide on endocrine reponses to female odour and reproductive behaviour in male parr of brown trout (Salmo trutta)
    Open this publication in new window or tab >>Effects of a pyrthroid pesticide on endocrine reponses to female odour and reproductive behaviour in male parr of brown trout (Salmo trutta)
    Show others...
    2007 (English)In: Aquatic Toxicology, ISSN 0166-445X, E-ISSN 1879-1514, Vol. 81, no 1, p. 1-9Article in journal (Refereed) Published
    Abstract [en]

    Reproductive behaviour of brown trout (Salmo trutta L.) from an anadromous stock was studied in a large stream water aquarium. Four adult males and two ovulated females were placed in the aquarium together with eight mature male parr. Four of the parr were exposed during the previous 4 days to two concentrations (0.1 or 1.0 μg l−1) of the pyrethroid pesticide cypermethrin (a disrupter of olfactory receptor function) and four of the parr to the solvent ethanol. The behaviour of all fish was followed for 24 h and then blood and milt was collected. Exposure to the higher concentration of cypermethrin disturbed the reproductive behaviour of the parr. They displayed fewer courting events, spent less time near the nesting females and had lower volumes of strippable milt. They also had significantly lower amounts of 11-ketotestosterone (11-KT) in the blood plasma than the control group. The higher cypermethrin group also had significantly lower levels of all these variables than the lower cypermethrin group, apart from strippable milt that showed no significant differences between two groups. No significant differences in non-reproductive behaviours were observed between any of the groups. In the control fish, there were significant positive correlations between (a) the number of courting events and the amount of time spent near the female, (b) blood plasma levels of 17α,20β-dihydroxy-4-pregnen-3-one (17,20β-P) and time spent near the female and (c) plasma levels of 17,20β-P and the number of courting events. Further, in control fish, higher plasma levels of 17,20β-P were observed in parr interacting with a female compared to those with no female contacts. A priming experiment confirmed a previous study that cypermethrin damages olfactory reception. Parr exposed to cypermethrin had significantly lower blood plasma levels of 17,20β-P and 11-KT than control males after exposure to ovarian fluid and urine (known to contain reproductive priming pheromones). When ethanol-exposed males were exposed to ovarian fluid and urine they had significantly higher plasma levels of 17,20β-P compared to those exposed to water only.

    Place, publisher, year, edition, pages
    Elsevier, 2007
    Keywords
    Cypermethrin, steroid, sex hormone, courting, spawning, Pheromones
    National Category
    Biological Sciences
    Research subject
    Toxicology; Biology with specialization in Animal Ecology
    Identifiers
    urn:nbn:se:uu:diva-122368 (URN)10.1016/j.aquatox.2006.10.011 (DOI)000244173200001 ()
    Projects
    Paper I
    Available from: 2010-04-09 Created: 2010-04-09 Last updated: 2017-12-12Bibliographically approved
    2. Effects of copper on olfactory-mediated endocrine responses and reproductive behaviour in mature male brown trout Salmo trutta parr to conspecific females
    Open this publication in new window or tab >>Effects of copper on olfactory-mediated endocrine responses and reproductive behaviour in mature male brown trout Salmo trutta parr to conspecific females
    2010 (English)In: Journal of Fish Biology, ISSN 0022-1112, E-ISSN 1095-8649, Vol. 76, no 4, p. 800-817Article in journal (Refereed) Published
    Abstract [en]

    In the present study, the effects of copper (CuSO4) on the ability of mature male brown trout Salmo trutta parr to detect and react both physiologically and behaviourally to female pheromones were studied. The study was composed of two parts. In the first experiment, priming effects of the female pheromone prostaglandin F (PGF) were evaluated by determining the amount of milt produced and the blood plasma levels of 11-ketotestosterone (11-KT) and 17α,20β-dihydroxy-4-pregnen-3-one (17,20β-P) after the PGF exposure. In the second experiment, male parr were placed in a large stream tank together with a group of adult males and ovulated females and their individual behaviours were recorded. In the priming experiment, the amount of expressible milt was significantly lower, less than half, in groups exposed during 4 days to 10 or 100 µg l−1 copper compared with control parr only exposed to water. No significant differences were observed in plasma levels of 11-KT and 17, 20β-P. During the behavioural experiment, exposed parr spent less time with the female and had a lower number of courting events. Blood plasma levels of 11-KT were, however, significantly higher in the group exposed to 100 µg l−1 copper compared with the control group. Furthermore, the exposed group spent significantly less time swimming upstream than did the control group. The present study demonstrates that exposure to copper affects reproductive behaviours and endocrinology of S. trutta male parr.

    Keywords
    hormones, olfaction, pheromones, pollutants, reproduction
    National Category
    Biological Sciences
    Identifiers
    urn:nbn:se:uu:diva-135856 (URN)10.1111/j.1095-8649.2009.02519.x (DOI)000275466200003 ()
    Note
    Corrigendum in: Journal of Fish Biology, 2010, vol. 76, issue 7, p. 1877, doi: 10.1111/j.1095-8649.2010.02687.x Available from: 2010-12-09 Created: 2010-12-08 Last updated: 2017-12-11Bibliographically approved
    3. Effects of glyphosate on olfactory mediated endorcine responses to female odours and reproductive behaviour in male brown trout (slamo trutta)
    Open this publication in new window or tab >>Effects of glyphosate on olfactory mediated endorcine responses to female odours and reproductive behaviour in male brown trout (slamo trutta)
    (English)In: Ecotoxicology, ISSN 0963-9292, E-ISSN 1573-3017Article in journal (Refereed) Submitted
    Keywords
    Glyphosate, behviour, pheromones, olfaction, reproduction
    National Category
    Zoology
    Research subject
    Biology with specialization in Animal Ecology
    Identifiers
    urn:nbn:se:uu:diva-122370 (URN)
    Projects
    Paper III
    Available from: 2010-04-09 Created: 2010-04-09 Last updated: 2017-12-12
    4. Prolonged cypermthrin exposure increases sex steroid plasma hormone levels in mature male brown trout (Salmo trutta) parr in spawning groups
    Open this publication in new window or tab >>Prolonged cypermthrin exposure increases sex steroid plasma hormone levels in mature male brown trout (Salmo trutta) parr in spawning groups
    (English)In: Aquatic Toxicology, ISSN 0166-445X, E-ISSN 1879-1514Article in journal (Refereed) Submitted
    Keywords
    Cypermethirn, behaviour, hormones, phermones, olfaction, reproduction
    National Category
    Zoology
    Research subject
    Biology with specialization in Animal Ecology
    Identifiers
    urn:nbn:se:uu:diva-122371 (URN)
    Projects
    Paper IV
    Available from: 2010-04-09 Created: 2010-04-09 Last updated: 2017-12-12
  • 154.
    Jaensson, Alia
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Olsén, K. Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Effects of copper on olfactory-mediated endocrine responses and reproductive behaviour in mature male brown trout Salmo trutta parr to conspecific females2010In: Journal of Fish Biology, ISSN 0022-1112, E-ISSN 1095-8649, Vol. 76, no 4, p. 800-817Article in journal (Refereed)
    Abstract [en]

    In the present study, the effects of copper (CuSO4) on the ability of mature male brown trout Salmo trutta parr to detect and react both physiologically and behaviourally to female pheromones were studied. The study was composed of two parts. In the first experiment, priming effects of the female pheromone prostaglandin F (PGF) were evaluated by determining the amount of milt produced and the blood plasma levels of 11-ketotestosterone (11-KT) and 17α,20β-dihydroxy-4-pregnen-3-one (17,20β-P) after the PGF exposure. In the second experiment, male parr were placed in a large stream tank together with a group of adult males and ovulated females and their individual behaviours were recorded. In the priming experiment, the amount of expressible milt was significantly lower, less than half, in groups exposed during 4 days to 10 or 100 µg l−1 copper compared with control parr only exposed to water. No significant differences were observed in plasma levels of 11-KT and 17, 20β-P. During the behavioural experiment, exposed parr spent less time with the female and had a lower number of courting events. Blood plasma levels of 11-KT were, however, significantly higher in the group exposed to 100 µg l−1 copper compared with the control group. Furthermore, the exposed group spent significantly less time swimming upstream than did the control group. The present study demonstrates that exposure to copper affects reproductive behaviours and endocrinology of S. trutta male parr.

  • 155.
    Jaensson, Alia
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Scott, Alexander
    Moore, Andrew
    Kylin, Henrik
    Olsén, K. Håkan
    Effects of a pyrthroid pesticide on endocrine reponses to female odour and reproductive behaviour in male parr of brown trout (Salmo trutta)2007In: Aquatic Toxicology, ISSN 0166-445X, E-ISSN 1879-1514, Vol. 81, no 1, p. 1-9Article in journal (Refereed)
    Abstract [en]

    Reproductive behaviour of brown trout (Salmo trutta L.) from an anadromous stock was studied in a large stream water aquarium. Four adult males and two ovulated females were placed in the aquarium together with eight mature male parr. Four of the parr were exposed during the previous 4 days to two concentrations (0.1 or 1.0 μg l−1) of the pyrethroid pesticide cypermethrin (a disrupter of olfactory receptor function) and four of the parr to the solvent ethanol. The behaviour of all fish was followed for 24 h and then blood and milt was collected. Exposure to the higher concentration of cypermethrin disturbed the reproductive behaviour of the parr. They displayed fewer courting events, spent less time near the nesting females and had lower volumes of strippable milt. They also had significantly lower amounts of 11-ketotestosterone (11-KT) in the blood plasma than the control group. The higher cypermethrin group also had significantly lower levels of all these variables than the lower cypermethrin group, apart from strippable milt that showed no significant differences between two groups. No significant differences in non-reproductive behaviours were observed between any of the groups. In the control fish, there were significant positive correlations between (a) the number of courting events and the amount of time spent near the female, (b) blood plasma levels of 17α,20β-dihydroxy-4-pregnen-3-one (17,20β-P) and time spent near the female and (c) plasma levels of 17,20β-P and the number of courting events. Further, in control fish, higher plasma levels of 17,20β-P were observed in parr interacting with a female compared to those with no female contacts. A priming experiment confirmed a previous study that cypermethrin damages olfactory reception. Parr exposed to cypermethrin had significantly lower blood plasma levels of 17,20β-P and 11-KT than control males after exposure to ovarian fluid and urine (known to contain reproductive priming pheromones). When ethanol-exposed males were exposed to ovarian fluid and urine they had significantly higher plasma levels of 17,20β-P compared to those exposed to water only.

  • 156. Johansson, Linda
    et al.
    Svensson, Linda
    Bergström, Ulrika
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology. Ekotoxikologi.
    Jacobsson-Ekman, Gunilla
    Arner, Elias S J
    van Hage, Marianne
    Bucht, Anders
    Gafvelin, Guro
    A mouse model for in vivo tracking of the major dust mite allergen Der p 2 after inhalation.2005In: FEBS J, ISSN 1742-464X, Vol. 272, no 13, p. 3449-60Article in journal (Refereed)
  • 157.
    Johansson, Maria
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Johansson, Niklas
    Lund, Bert-Ove
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Xenobiotics and the glucocorticoid receptor: additive antagonistic effects on tyrosine aminotransferase activity in rat hepatoma cells.2005In: Basic Clin Pharmacol Toxicol, ISSN 1742-7835, Vol. 96, no 4, p. 309-15Article in journal (Refereed)
  • 158.
    Johansson, Niclas
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Neonatal Exposure to Highly Brominated Diphenyl Ethers and Perfluorinated Compounds: Developmental Dependent Toxicity and Interaction2009Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis investigated the developmental neurotoxic effects of neonatal exposure to highly brominated diphenyl ethers (PBDEs) and perfluorinated compounds (PFCs), alone or in combinations, during a critical period of the brains’ rapid growth and development, in mice. The compounds investigated were the decaBDE (PBDE 209), nonaBDE (PBDE 206), octaBDE (PBDE 203), heptaBDE (PBDE 183), and three PFCs, PFOS, PFOA, and PFDA.

    PBDEs and PFCs have been identified as emerging classes of persistent environmental compounds, present in wildlife as well as humans, and present at higher levels in infants/children, compared to older persons. Individuals can be exposed to these compounds throughout her/his lifetime and newborn/children can be exposed to toxicants both via the mothers’ milk and directly via ingestion and inhalation.

    The brain growth spurt (BGS) is defined by rapid growth and developmental of the brain. For rodents (mice and rats), the BGS is postnatal spanning the first 3-4 weeks after birth. In humans this period begins during the third trimester of pregnancy and continues throughout the first two years of life. It has been shown that several environmental toxicants can induce permanent disorders in brain function when administered to the neonatal mouse, during the BGS.

    This thesis shows that highly brominated PBDEs, including PBDE 209, PBDE 206, and PBDE 203 can cause developmental neurotoxic effects, when given directly to the neonatal mouse. Of the investigated PFCs, PFOS and PFOA were shown to cause similar effects as the PBDEs. Furthermore, PBDE 209 and PFOA can at low doses interact and enhance the neurotoxic effects in mice. Effects in the adult animal included; deranged spontaneous behavior, reduced or lack of habituation, decreased learning and memory abilities, and increased susceptibility of the cholinergic system. Both classes of compounds were shown to affect proteins (CaMKII, GAP-43, synaptophysin, and tau) important for neuronal growth and synaptogenesis in the neonatal mouse brain.

    List of papers
    1. Neontatal exposure to deca-brominated diphenyl ether (PBDE 209) causes dose-response changes in spontaneous behaviour and cholinergic susceptibility in adult mice
    Open this publication in new window or tab >>Neontatal exposure to deca-brominated diphenyl ether (PBDE 209) causes dose-response changes in spontaneous behaviour and cholinergic susceptibility in adult mice
    2008 (English)In: Neurotoxicology, ISSN 0161-813X, E-ISSN 1872-9711, Vol. 29, no 6, p. 911-919Article in journal (Refereed) Published
    Abstract [en]

    Polybrominated diphenyl ethers (PBDEs), used as additive flame-retardants, are increasing in the environment and are present in human mother's milk, newborns and toddlers. We reported earlier that several PBDEs, highly brominated PBDEs, caused developmental neurotoxic effects in mice, manifested as persistent aberrations in spontaneous behaviour, habituation capability, learning and memory, and changes in the cholinergic system.The present study was undertaken to explore the dose–response effects of PBDE 209 on spontaneous behaviour, habituation and its effects on the murine cholinergic system. Neonatal male NMRI mice were given 1.4, 2.3, 14 or 21 μmol PBDE 209/kg body weight, when 3 days old. The agent was administered as a single oral dose via a metal gastric tube. Spontaneous behaviour and response to the cholinergic agonist nicotine were observed in adult mice at 2 and 4 months of age. Mice were also observed for anxiety-like behaviour in an elevated plus-maze. Adult mice, 2 and 4 months old, showed a dose–response related change in spontaneous behaviour, viz. were hyperactive and showed reduced or lack of habituation, effects that worsen with age. At the adult age of 4 months the susceptibility of the cholinergic system was also affected in a dose–response related manner, viz. reduced and/or hypoactive response to nicotine. This shows that PBDE 209 can be as potent as the lower brominated PBDEs in causing developmental neurotoxic defects.

    Keywords
    Deca-brominated diphenyl ether, Flame-retardant, Neonatal, Spontaneous behaviour, Cholinergic, PBDE 209
    National Category
    Pharmacology and Toxicology
    Identifiers
    urn:nbn:se:uu:diva-99061 (URN)10.1016/j.neuro.2008.09.08 (DOI)000261551800001 ()
    Available from: 2009-03-06 Created: 2009-03-06 Last updated: 2018-01-13Bibliographically approved
    2. Neonatal exposure to higher brominated diphenyl ethers, hepta-, octa-, or nonabromodiphenyl ether, impaires spontaneous behavior and learning and memory functions of adult mice
    Open this publication in new window or tab >>Neonatal exposure to higher brominated diphenyl ethers, hepta-, octa-, or nonabromodiphenyl ether, impaires spontaneous behavior and learning and memory functions of adult mice
    Show others...
    2006 (English)In: Toxicological Sciences, Vol. 92, p. 211-18Article in journal (Refereed) Published
    Identifiers
    urn:nbn:se:uu:diva-21970 (URN)
    Available from: 2007-01-23 Created: 2007-01-23 Last updated: 2011-01-11
    3. Neonatal exposure to perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) causes neurobehavioural defects in adult mice
    Open this publication in new window or tab >>Neonatal exposure to perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) causes neurobehavioural defects in adult mice
    2008 (English)In: Neurotoxicology, ISSN 0161-813X, E-ISSN 1872-9711, Vol. 29, no 1, p. 160-169Article in journal (Refereed) Published
    Abstract [en]

    Perfluorinated compounds (PFCs) are found in applications such oil/water repellents for clothing fabrics, carpets, food packaging, lubricants, surfactants and fire extinguishers. PFCs are persistent in the environment. They have been found in humans and in wildlife.

    We reported earlier that persistent organic pollutants (POPs), such as DDT, PCBs and BFRs, caused developmental neurotoxic defects in mice, manifested as persistent aberrations in spontaneous behaviour, habituation capability, learning and memory, and changes in the cholinergic system in adults, when mice were exposed during a critical period of neonatal brain development.The present study was conducted to see whether PFCs can cause similar developmental neurotoxic effects as earlier observed for POPs as PCBs and PBDEs. NMRI male mice were exposed to a single-oral dose, either 1.4 or 21 μmol/kg body weight of PFOS (0.75 or 11.3 mg), PFOA (0.58 or 8.70 mg), or PFDA (0.72 or 10.8 mg), via a metal gastric-tube at the age of 10 days. The control animals received in the same manner 10 ml/kg body weight of the 20% fat emulsion vehicle. Spontaneous behaviour (locomotion, rearing, and total activity), and habituation were observed in 2- and 4-month-old mice. The susceptibility of the cholinergic system was explored in a nicotine-induced spontaneous behaviour test in 4-month-old mice. Deranged spontaneous behaviour was observed in mice exposed to PFOS and PFOA, manifested as reduced and/or lack of habituation and hyperactivity in adult mice. These effects were also seen to worse with age. Neonatal exposure to PFOS and PFOA affected the cholinergic system, manifested as a hypoactive response to nicotine, compared to a hyperactive response to nicotine in controls. These developmental neurotoxic effects are similar to those we reported earlier for PCBs and PBDEs. This suggests that PFOS and PFOA be included in the group of POPs known to be developmental neurotoxicants.

    Keywords
    PFC, PFOS, PFOA, PFDA, Developmental neurotoxicity, Behaviour
    National Category
    Pharmacology and Toxicology
    Identifiers
    urn:nbn:se:uu:diva-12791 (URN)10.1016/j.neuro.2007.10.008 (DOI)000253187600019 ()18063051 (PubMedID)
    Available from: 2008-06-12 Created: 2008-06-12 Last updated: 2018-01-12Bibliographically approved
    4.
    The record could not be found. The reason may be that the record is no longer available or you may have typed in a wrong id in the address field.
    5. Highly brominated diphenyl ethers (PBDE 209) can by interacting with perfluorinated chemicals (PFOA) during neonatal brain development, exacerbate neurobehavioural defects
    Open this publication in new window or tab >>Highly brominated diphenyl ethers (PBDE 209) can by interacting with perfluorinated chemicals (PFOA) during neonatal brain development, exacerbate neurobehavioural defects
    (English)Manuscript (Other (popular science, discussion, etc.))
    Identifiers
    urn:nbn:se:uu:diva-99075 (URN)
    Available from: 2009-03-06 Created: 2009-03-06 Last updated: 2010-01-14
    6. PBDE 209 and PFOA interact during neonatal brain development affecting developmental marker proteins synaptophysin and tau levels in the neonatal mouse
    Open this publication in new window or tab >>PBDE 209 and PFOA interact during neonatal brain development affecting developmental marker proteins synaptophysin and tau levels in the neonatal mouse
    (English)Manuscript (Other academic)
    Identifiers
    urn:nbn:se:uu:diva-99068 (URN)
    Available from: 2009-03-06 Created: 2009-03-06 Last updated: 2010-01-14
  • 159.
    Johansson, Niclas
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Eriksson, Per
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Viberg, Henrik
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Neonatal exposure to PFOS and PFOA in mice results in changes in proteins which are important for neuronal growth and synaptogenesis in the developing brain2009In: Toxicological Sciences, ISSN 1096-6080, E-ISSN 1096-0929, Vol. 108, no 2, p. 412-418Article in journal (Refereed)
    Abstract [en]

    Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) belong to the family of perfluorinated compounds (PFCs). They are used in industrial and consumer applications, e.g. clothing fabrics, carpets and food packaging. PFOS and PFOA are present in the environment and are found in dust and human milk, which implies that newborns and toddlers can be directly exposed to these agents during brain development. Recently, we reported that PFOS and PFOA can cause neurobehavioral defects and changes in the cholinergic system, in the adult animal, when given directly to neonatal mice, and thereby showing similarities with other investigated persistent organic pollutants (POPs), such as DDT, polychlorinated biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs). In recent studies, we have also seen that highly brominated PBDEs can affect the levels of proteins that are important for neuronal growth and synaptogenesis in the neonatal mouse brain. The present study shows that a single oral dose of either 21 µmol PFOS or PFOA/kg body weight (11.3 mg or 8.70 mg), given directly to the neonatal mice on postnatal day 10, significantly increased the levels of CaMKII, GAP-43, and synaptophysin in the hippocampus of the neonatal mouse. Both compounds significantly increased the levels of synaptophysin and tau in cerebral cortex and PFOA also increased the levels of tau in hippocampus. Since these proteins are important for normal brain development and altered levels of these proteins during a critical period of the brain growth spurts (BGS) could be one of the mechanisms behind earlier reported behavioral defects.

  • 160.
    Johansson, Niclas
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Fredriksson, A
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Eriksson, Per
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Neonatal exposure to perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) causes neurobehavioural defects in adult mice2008In: Neurotoxicology, ISSN 0161-813X, E-ISSN 1872-9711, Vol. 29, no 1, p. 160-169Article in journal (Refereed)
    Abstract [en]

    Perfluorinated compounds (PFCs) are found in applications such oil/water repellents for clothing fabrics, carpets, food packaging, lubricants, surfactants and fire extinguishers. PFCs are persistent in the environment. They have been found in humans and in wildlife.

    We reported earlier that persistent organic pollutants (POPs), such as DDT, PCBs and BFRs, caused developmental neurotoxic defects in mice, manifested as persistent aberrations in spontaneous behaviour, habituation capability, learning and memory, and changes in the cholinergic system in adults, when mice were exposed during a critical period of neonatal brain development.The present study was conducted to see whether PFCs can cause similar developmental neurotoxic effects as earlier observed for POPs as PCBs and PBDEs. NMRI male mice were exposed to a single-oral dose, either 1.4 or 21 μmol/kg body weight of PFOS (0.75 or 11.3 mg), PFOA (0.58 or 8.70 mg), or PFDA (0.72 or 10.8 mg), via a metal gastric-tube at the age of 10 days. The control animals received in the same manner 10 ml/kg body weight of the 20% fat emulsion vehicle. Spontaneous behaviour (locomotion, rearing, and total activity), and habituation were observed in 2- and 4-month-old mice. The susceptibility of the cholinergic system was explored in a nicotine-induced spontaneous behaviour test in 4-month-old mice. Deranged spontaneous behaviour was observed in mice exposed to PFOS and PFOA, manifested as reduced and/or lack of habituation and hyperactivity in adult mice. These effects were also seen to worse with age. Neonatal exposure to PFOS and PFOA affected the cholinergic system, manifested as a hypoactive response to nicotine, compared to a hyperactive response to nicotine in controls. These developmental neurotoxic effects are similar to those we reported earlier for PCBs and PBDEs. This suggests that PFOS and PFOA be included in the group of POPs known to be developmental neurotoxicants.

  • 161.
    Johansson, Niclas
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Fredriksson, Anders
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Eriksson, Per
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Highly brominated diphenyl ethers (PBDE 209) can by interacting with perfluorinated chemicals (PFOA) during neonatal brain development, exacerbate neurobehavioural defectsManuscript (Other (popular science, discussion, etc.))
  • 162.
    Johansson, Niclas
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology. Ekotoxikologi.
    Fredriksson, Anders
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology. Ekotoxikologi.
    Eriksson, Per
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology. Ekotoxikologi.
    Highly brominated diphenyl ethers (PBDE 209) interact with the perfluorooctanoic acid (PFOA) during neonatal brain development to enhance developmental neurobehavioural defects2007In: The Toxicologist, 2007Conference paper (Refereed)
  • 163.
    Johansson, Niclas
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Fredriksson, Anders
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Eriksson, Per
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Neonatal exposure to perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) causes deranged behaviour and increased susceptibility of the cholinergic system in adult mice2006In: The Toxicologist, 2006, p. 1458-Conference paper (Refereed)
  • 164.
    Johansson, Niclas
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Viberg, Henrik
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Fredriksson, Anders
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Eriksson, Per
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Neonatal exposure to polybrominated diphenyl ethers, PBDE 183, PBDE 203, and PBDE 206, causes neurotoxic effects in adult mice2005In: Toxicologist 84, 2005, p. 2062-Conference paper (Refereed)
  • 165.
    Johansson, Niclas
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Viberg, Henrik
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Fredriksson, Anders
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Eriksson, Per
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Neontatal exposure to deca-brominated diphenyl ether (PBDE 209) causes dose-response changes in spontaneous behaviour and cholinergic susceptibility in adult mice2008In: Neurotoxicology, ISSN 0161-813X, E-ISSN 1872-9711, Vol. 29, no 6, p. 911-919Article in journal (Refereed)
    Abstract [en]

    Polybrominated diphenyl ethers (PBDEs), used as additive flame-retardants, are increasing in the environment and are present in human mother's milk, newborns and toddlers. We reported earlier that several PBDEs, highly brominated PBDEs, caused developmental neurotoxic effects in mice, manifested as persistent aberrations in spontaneous behaviour, habituation capability, learning and memory, and changes in the cholinergic system.The present study was undertaken to explore the dose–response effects of PBDE 209 on spontaneous behaviour, habituation and its effects on the murine cholinergic system. Neonatal male NMRI mice were given 1.4, 2.3, 14 or 21 μmol PBDE 209/kg body weight, when 3 days old. The agent was administered as a single oral dose via a metal gastric tube. Spontaneous behaviour and response to the cholinergic agonist nicotine were observed in adult mice at 2 and 4 months of age. Mice were also observed for anxiety-like behaviour in an elevated plus-maze. Adult mice, 2 and 4 months old, showed a dose–response related change in spontaneous behaviour, viz. were hyperactive and showed reduced or lack of habituation, effects that worsen with age. At the adult age of 4 months the susceptibility of the cholinergic system was also affected in a dose–response related manner, viz. reduced and/or hypoactive response to nicotine. This shows that PBDE 209 can be as potent as the lower brominated PBDEs in causing developmental neurotoxic defects.

  • 166.
    Jönsson, E. Maria
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Brunström, Björn
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Ingebrigtsen, Kristian
    Brandt, Ingvar
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Cell-specific CYP1A expression and benzo(a)pyrene adduct formation in gills of rainbow trout (Oncorhynchus mykiss ) following CYP1A induction in the laboratory and in the field2004In: Environmental Toxicology and Chemistry, ISSN 0730-7268, E-ISSN 1552-8618, Vol. 23, no 4, p. 874-882Article in journal (Refereed)
    Abstract [en]

    The effect of cytochrome P4501A (CYP1A)induction on cell-specific benzo[a]pyrene (BaP) adduct formation was studied in rainbow trout (Oncorhynchus mykiss) gills. Fish preexposed to β-naphthoflavone (βNF) or caged in a polluted river were exposed to waterborne 3H-benzo[a]pyrene (3H-BaP). The 3H-benzo[a]pyrene adducts in the gill filaments were localized by autoradiography and CYP1A protein by immunohistochemistry. Ethoxyresorufin O-deethylase (EROD) activity was measured using a gill filament-based ex vivo assay. Branchial 3H-BaP binding and EROD activity were enhanced by exposure to βNF or to the river water, and completely blocked by the CYP1A inhibitor ellipticine. The predominant sites of adduct formation were in epithelium of the secondary lamellae and in epithelium of the efferent edge of the gill filament. In βNF-exposed fish, the strongest CYP1A immunoreactivity was observed in differentiating cells and in pillar cells. In fish caged in the polluted river, strong CYP1A immunoreactivity was found in most cells in the secondary lamellae, whereas the primary lamellae were almost devoid of immunoreactivity. Our results reveal a discrepancy between the localization of CYP1A protein and BaP adducts in the gill. Consequently, other factors, such as bioavailability of waterborne polycyclic aromatic hydrocarbons (PAHs) to the target cells, are important for the localization of PAH adducts in the gill.

  • 167.
    Jönsson, Maria
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Abrahamson, Alexandra
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Brunström, Björn
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Brandt, Ingvar
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Cytochrome P4501A induction in rainbow trout gills and liver following exposure to waterborne indigo, benzo(a)pyrene and 3,3',4,4',5-pentachlorobiphenyl2006In: Aquatic Toxicology, ISSN 0166-445X, E-ISSN 1879-1514, Vol. 79, no 3, p. 226-232Article in journal (Refereed)
    Abstract [en]

    We have developed a gill-filament based ethoxyresorufin O-deethylase (EROD) assay to be used as a tool to monitor cytochrome P4501A (CYP1A) induction in caged fish. The present study aimed to compare temporal patterns of EROD induction in gills and liver of rainbow trout (Oncorhynchus mykiss) exposed in the laboratory to readily metabolized and persistent CYP1A inducers, i.e. indigo, benzo[a]pyrene (BaP), and 3,3',4,4',5-pentachlorobiphenyl (PCB#126). Branchial and hepatic EROD activities were examined in fish exposed for 6, 12, or 24h and in fish exposed for 24h and then held in clean water for 2 or 14 days. Furthermore, branchial CYP1A protein expression was localized by immunohistochemistry. All compounds strongly induced branchial EROD activity within 6 h. The highest EROD inductions observed for indigo, BaP, and PCB#126 were roughly similar in gills (52-, 76-, and 74-fold), but differed considerably in liver (11-, 78-, and 200-fold). In indigo- and BaP-exposed fish, both hepatic and branchial EROD activities decreased rapidly in clean water. In PCB#126-exposed fish, decreased branchial and increased hepatic EROD activities were observed following transfer to clean water. The substances gave rise to immunostaining for CYP1A at different cellular sites. All inducers increased the CYP1A-immunostaining in the gill filament secondary lamellae, but PCB#126 also induced a pronounced CYP1A immunoreactivity in cells near the basal membrane of the epithelium of the primary lamellae. The observation that the low BaP and indigo concentrations induced EROD activity markedly in the gills but only slightly or not at all in the liver, supports the contention that readily metabolized AhR agonists may escape detection when hepatic EROD activity is used for environmental monitoring. The results show that gill filament EROD activity is a sensitive biomarker both for persistent and readily metabolized AhR agonists in polluted water.

  • 168. Jönsson, Maria
    et al.
    Abrahamson, Alexandra
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Brunström, Björn
    Brandt, Ingvar
    Ingebrigtsen, Kristian
    Jørgensen, Even H.
    EROD activity in gill filaments from anadromous and marine fish as a biomarker of dioxin-like pollutants2003In: Comparative Biochemistry and Physiology Part C, Vol. 136, p. 235-243Article in journal (Refereed)
  • 169.
    Jönsson, Maria
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Abrahamson, Alexandra
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Brunström, Björn
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Brandt, Ingvar
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Ingebrigtsen, Kristian
    Jørgensen, Even H
    EROD activity in gill filaments of anadromous and marine fish as a biomarker of dioxin-like pollutants.2003In: Comp Biochem Physiol C Toxicol Pharmacol, ISSN 1532-0456, Vol. 136, no 3, p. 235-43Article in journal (Refereed)
  • 170.
    Jönsson, Maria
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Brandt, Ingvar
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Brunström, Björn
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    A gill filament-based EROD assay for monitoring waterborne dioxin-like pollutants in fish.2002In: Environmental Science and Technology, Vol. 36, p. 3340-3344Article in journal (Refereed)
  • 171.
    Jönsson, Maria E
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Brunström, Björn
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Brandt, Ingvar
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    The zebrafish gill model: induction of CYP1A, EROD and PAH adduct formation2009In: Aquatic Toxicology, ISSN 0166-445X, E-ISSN 1879-1514, Vol. 91, no 1, p. 62-70Article in journal (Refereed)
    Abstract [en]

    Zebrafish (Danio rerio) is a common model species in fish toxicology, and the zebrafish gill is potentially useful in screening waterborne pollutants. We have previously developed a gill-based ethoxyresorufin-O-deethylase (EROD) assay, and proposed gill EROD activity as a biomarker for exposure to waterborne aryl hydrocarbon receptor (AHR) agonists. In this study we modified the gill EROD assay for use in zebrafish. We used immunohistochemistry to localize CYP1A induction, and microautoradiography to localize irreversible binding of the prototypic polycyclic aromatic hydrocarbon, 7,12-dimethylbenz[a]anthracene (DMBA) in zebrafish gills. Gill filament and liver microsomal EROD activities were measured after waterborne exposure of zebrafish and rainbow trout to benzo[a]pyrene (BaP) or beta-naphthoflavone (betaNF). The results showed considerably lower relative EROD induction by betaNF (1microM) in zebrafish than in rainbow trout, both in gills (13-fold versus 230-fold compared to control) and in liver (5-fold versus 320-fold compared to control). The induced hepatic EROD activity was similar in the two species, whereas the basal activity was considerably higher in zebrafish than in rainbow trout. In zebrafish gills, betaNF enhanced DMBA adduct formation and CYP1A immunostaining. Ellipticine blocked DMBA adduct formation and EROD activity following betaNF exposure but had no effect on CYP1A immunostaining. A notable finding was that the localization of DMBA adducts differed from that of CYP1A protein in betaNF-induced fish; CYP1A immunoreactivity was evenly distributed in the gills whereas DMBA adduction was confined to the leading edges of the filaments and the gill rakers, i.e., structures being highly exposed to DMBA-containing inhaled water. The results show that the modified method is suitable for determination of gill EROD activity in zebrafish, although rainbow trout seems more sensitive. They also imply that the sites of DMBA adduct formation in zebrafish gills are markedly influenced by kinetic factors.

  • 172.
    Jönsson, Maria E.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Carlsson, Carina
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Smith, Richard W.
    Pärt, Peter
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Effects of copper on CYP1A activity and epithelial barrier properties in the rainbow trout gill2006In: Aquatic Toxicology, ISSN 0166-445X, E-ISSN 1879-1514, Vol. 79, no 1, p. 78-86Article in journal (Refereed)
    Abstract [en]

    The effects of copper on P-naphthoflavone (beta NF)-induced ethoxyresorufin O-deethylase (EROD) activity were studied in rainbow trout (Oncorhynchus mykiss) gill filaments (after in vivo exposure) and in gill cells cultured as both primary cultures and as polarised epithelia, i.e. with water in the apical compartment and culture medium in the basolateral compartment. In the in vivo study beta NF and copper were added to the water, in primary cultures both chemicals were added to the culture medium and in cultured epithelia copper was added to the apical water whilst beta NF was added to the basolateral culture medium. In primary cultures this investigation was repeated with and without foetal bovine serum (FBS) supplementation of the culture media. Gill barrier properties, specifically polyethylene glycol (PEG-4000) permeability (i.e. paracellular permeability), sodium efflux and transepithelial electrical resistance (TER) were also investigated in cultured gill cell epithelia after apical treatment with copper. Two micromolar copper had no effect on EROD activity in gill filaments in vivo irrespective of whether EROD was induced by 0.01, 0.1 or 1.0 mu M beta NF Similarly, 0.5-100 mu M copper had no effect on EROD induction in cultured epithelia. In primary cultures copper did reduce EROD induction but the effective concentration was dependent on whether the cells were supplemented with FBS, i.e. EROD activity was reduced by all copper concentrations of 5 and above if FBS was included, but only by 1000 mu M if FBS was omitted. In cultured epithelia PEG-4000 permeability increased, whilst sodium efflux and TER were unaffected following treatment with 75 mu M copper. Based on these results we conclude that the branchial monooxygenase system is a less sensitive target for copper than the barrier properties of the gill. Indeed, these data suggest the apical membrane of the gill epithelial cells minimises the uptake of waterborne copper and therefore protects the intracellular environment, including the CYP1A system. This could enable the freshwater fish gill to retain their potential of first-pass metabolism of waterborne organic compounds whilst simultaneously being exposed to waterborne copper.

  • 173.
    Jönsson, Maria E
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Franks, Diana G
    Woodin, Bruce R
    Jenny, Matthew J
    Garrick, Rita A
    Behrendt, Lars
    Hahn, Mark E
    Stegeman, John J
    The tryptophan photoproduct 6-formylindolo[3,2-b]carbazole (FICZ) binds multiple AHRs and induces multiple CYP1 genes via AHR2 in zebrafish2009In: Chemico-Biological Interactions, ISSN 0009-2797, E-ISSN 1872-7786, Vol. 181, no 3, p. 447-454Article in journal (Refereed)
    Abstract [en]

    The tryptophan photooxidation product 6-formylindolo[3,2-b]carbazole (FICZ) has been proposed as a physiological ligand for the mammalian aryl hydrocarbon receptor (AHR), which it binds with high-affinity, inducing expression of cytochrome P450 1A1 (CYP1A1). We investigated whether the response to FICZ is evolutionarily conserved in vertebrates by measuring FICZ binding to two zebrafish AHRs (AHR1B and AHR2) and its ability to induce zebrafish CYP1 genes (CYP1A, CYP1B1, CYP1C1, CYP1C2, and CYP1D1) in vivo. Exposure of zebrafish embryos (48h-post-fertilization; hpf) to 10nM FICZ for 6h caused strong induction of CYP1A mRNA and a statistically significant but modest induction of CYP1B1 and CYP1C1. Neither CYP1C2 nor CYP1D1 expression was induced by FICZ under the conditions of dose, time or developmental stage examined here. CYP1A induction was significantly greater after 6h than after 12h of exposure to FICZ, suggesting a rapid degradation of inducer. The 6-h EC(50) values for induction of CYP1A and CYP1B1 by FICZ were 0.6 and 0.5nM compared to 72-h EC(50) values of 2.3 and 2.7nM for PCB126, indicating that in zebrafish embryos FICZ is a more potent inducer than PCB126. FICZ at 10nM was able to completely displace binding of 2,3,7,8-tetrachloro-1,6[(3)H]-dibenzo-p-dioxin to in vitro-expressed zebrafish AHR2 and AHR1B. Inhibition of AHR2 translation in zebrafish embryos by an AHR2-specific morpholino antisense oligonucleotide decreased the induction of CYP1A and CYP1B1 by FICZ and by PCB126. Together, these results demonstrate that FICZ is a potent AHR agonist in zebrafish, inducing expression of multiple CYP1 genes largely through AHR2. Evolutionary conservation of the response to FICZ is consistent with a possible role as an endogenous signaling molecule acting through the AHR.

  • 174.
    Jönsson, Maria E.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Jenny, Matthew J.
    Woodin, Bruce R.
    Hahn, Mark E.
    Stegeman, John J.
    Role of AHR2 in the expression of novel cytochrome P450 1 family genes, cell cycle genes, and morphological defects in developing zebra fish exposed to 3,3′,4,4′,5-pentachlorobiphenyl or 2,3,7,8-tetrachlorodibenzo- p -dioxin2007In: Toxicological Sciences, ISSN 1096-6080, E-ISSN 1096-0929, Vol. 100, no 1, p. 180-193Article in journal (Refereed)
    Abstract [en]

    Halogenated agonists for the aryl hydrocarbon receptor (AHR), such as 3,3',4,4',5-pentachlorobiphenyl (PCB126) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), cause developmental toxicity in fish. AHR dependence of these effects is known for TCDD but only presumed for PCB126, and the AHR-regulated genes involved are known only in part. We defined the role of AHR in regulation of four cytochrome P450 1 (CYP1) genes and the effect of PCB126 on cell cycle genes (i.e., PCNA and cyclin E) in zebra fish (Danio rerio) embryos. Basal and PCB126-induced expression of CYP1A, CYP1B1, CYP1C1, and CYP1C2 was examined over time as well as in relation to cell cycle gene expression and morphological effects of PCB126 in developing zebra fish. The four CYP1 genes differed in the time for maximal basal and induced expression, i.e., CYP1B1 peaked within 2 days postfertilization (dpf), the CYP1Cs around hatching (3 dpf), and CYP1A after hatching (14–21 dpf). These results indicate developmental periods when the CYP1s may play physiological roles. PCB126 (0.3–100nM) caused concentration-dependent CYP1 gene induction (EC50: 1.4–2.7nM, Lowest observed effect concentration [LOEC]: 0.3–1nM) and pericardial edema (EC50: 4.4nM, LOEC: 3nM) in 3-dpf embryos. Blockage of AHR2 translation significantly inhibited these effects of PCB126 and TCDD. PCNA gene expression was reduced by PCB126 in a concentration-dependent manner, suggesting that PCB126 could suppress cell proliferation. Our results indicate that the four CYP1 genes examined are regulated by AHR2 and that the effect of PCB126 on morphology in zebra fish embryos is AHR2 dependent. Moreover, the developmental patterns of expression and induction suggest that CYP1 enzymes could function in normal development and in developmental toxicity of PCB126 in fish embryos.

  • 175.
    Jönsson, Maria E.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Orrego, Rodrigo
    Woodin, Bruce R.
    Goldstone, Jared V.
    Stegeman, John J.
    Basal and 3,3',4,4',5-pentachlorobiphenyl-induced expression of cytochrome P450 1A, 1B and 1C genes in zebrafish2007In: Toxicology and Applied Pharmacology, ISSN 0041-008X, E-ISSN 1096-0333, Vol. 221, no 1, p. 29-41Article in journal (Refereed)
    Abstract [en]

    The cytochrome P4501C (CYP1C) gene subfamily was recently discovered in fish, and zebrafish (Danio rerio) CYP1C1 transcript has been cloned. Here we cloned the paralogous CYP1C2, showing that the amino acid sequence is 78% identical to CYP1C1, and examined gene structure and expression of CYP1A, CYP1B1, CYP1C1, and CYP1C2. Xenobiotic response elements were observed upstream of the coding regions in all four genes. Zebrafish adults and embryos were exposed (24 h) to 100 nM 3,3′,4,4′,5-polychlorinated biphenyl (PCB126) or 20 ppm acetone and subsequently held in clean water for 24 h (adults) or 48 h (embryos). All adult organs examined (eye, gill, heart, liver, kidney, brain, gut, and gonads) and embryos showed basal expression of the four genes. CYP1A was most strongly expressed in liver, whereas CYP1B1, CYP1C1, and CYP1C2 were most strongly expressed in heart and eye. CYP1B1 and the CYP1C genes showed an expression pattern similar to one another and to mammalian CYP1B1. In embryos CYP1C1 and CYP1C2 tended to have a higher basal expression than CYP1A and CYP1B1. PCB126 induced CYP1A in all organs, and CYP1B1 and CYP1C1 in all organs except gonads, or gonads and brain, respectively. CYP1C2 induction was significant only in the liver. However, in embryos all four genes were induced strongly by PCB126. The results are consistent with CYP1C1 and CYP1C2, as well as CYP1A and CYP1B1, being regulated by the aryl hydrocarbon receptor. While CYP1A may have a protective role against AHR agonists in liver and gut, CYP1B1, CYP1C1, and CYP1C2 may also play endogenous roles in eye and heart and possibly other organs, as well as during development.

  • 176.
    Karlsson, Oskar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Berg, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Brittebo, Eva B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Lindquist, Nils Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Retention of the cyanobacterial neurotoxin beta-N-methylamino-l-alanine in melanin and neuromelanin-containing cells: a possible link between Parkinson-dementia complex and pigmentary retinopathy2009In: Pigment cell & melanoma research, ISSN 1755-1471, Vol. 22, no 1, p. 120-130Article in journal (Refereed)
    Abstract [en]

    beta-N-methylamino-l-alanine (BMAA), a neurotoxic amino acid produced by cyanobacteria, has been suggested to be involved in the etiology of a neurodegenerative disease complex which includes Parkinson-dementia complex (PDC). In PDC, neuromelanin-containing neurons in substantia nigra are degenerated. Many PDC patients also have an uncommon pigmentary retinopathy. The aim of this study was to investigate the distribution of (3)H-BMAA in mice and frogs, with emphasis on pigment-containing tissues. Using autoradiography, a distinct retention of (3)H-BMAA was observed in melanin-containing tissues such as the eye and neuromelanin-containing neurons in frog brain. Analysis of the binding of (3)H-BMAA to Sepia melanin in vitro demonstrated two apparent binding sites. In vitro-studies with synthetic melanin revealed a stronger interaction of (3)H-BMAA with melanin during synthesis than the binding to preformed melanin. Long-term exposure to BMAA may lead to bioaccumulation in melanin- and neuromelanin-containing cells causing high intracellular levels, and potentially changed melanin characteristics via incorporation of BMAA into the melanin polymer. Interaction of BMAA with melanin may be a possible link between PDC and pigmentary retinopathy.

  • 177.
    Lind, Monica
    et al.
    Institute of Environmental Medicine, Karolinska Institutet.
    Bergman, Anders
    Olsson, Mats
    Örberg, Jan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Bone mineral density in male Baltic grey seal (Halichoerus grypus)2003In: Ambio, ISSN 0044-7447, E-ISSN 1654-7209, Vol. 32, no 6, p. 385-388Article in journal (Refereed)
    Abstract [en]

    Bone mineral density (mg cm(-3)) was studied in male Baltic grey seals (4-23 years of age) by noninvasive computed tomography (pQCT). The material was grouped according to year of collection. Group A: 1850-1955, a period before the main introduction of organochlorines (OCs); Group B: 1965-1985, a period with very high OC contamination; and Group C: 1986-1997, a period with decreasing concentrations of OCs. The reproducibility of the measurements was good with a Coefficient of Variation (CV) ranging from 0.1% to 2.1%. Trabecular bone mineral density of the radius was significantly higher in specimens collected 1986-1997 than in those collected 1965-1985 (p < 0.05). Cortical bone mineral density of the mandible was significantly lower in specimens collected 1986-1997 compared with those collected 1850-1955 (p < 0.05). These results indicate different responses over time in trabecular and cortical bone. During the period of very high OC contamination (1965-1985), trabecular bone density was lowest, whereas cortical bone density was lowest in specimens collected 1985-1997, representing a period of fairly low OC contamination. The mechanisms behind these effects are not known. However, it can be assumed that OCs are involved. Information about residue levels of OCs in the studied individuals is lacking and, therefore, it was not possible to evaluate the impact of OCs in this respect.

  • 178.
    Lind, Monica
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolutionary Biology.
    Eriksen, E F
    Sahlin, L
    Edlund, M
    Örberg, J
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Effects of the antiestrogenic environmental pollutant 3,3',4,4', 5-pentachlorobiphenyl (PCB #126) in rat bone and uterus: diverging effects in ovariectomized and intact animals1999In: Toxicology and Applied Pharmacology, ISSN 0041-008X, E-ISSN 1096-0333, Vol. 154, no 3, p. 236-244Article in journal (Other academic)
    Abstract [en]

    The purpose of this study was to compare effects on rat bone and uterus of estrogen depletion and exposure to the coplanar PCB-congener 3,3',4,4',5-pentachlorobiphenyl (PCB #126) which exhibits anti-estrogenic properties. Half of the rats were ovariectomized (n = 20) and the other half were sham-operated. Ten of the ovariectomized rats and ten of the sham operated were exposed to PCB #126 (ip injections) for 3 months (total dose: 384 microgram/kg body wt). The remaining control rats were injected with corn oil (vehicle). The rats were killed and the tibiae and uteri were dissected. The left tibia was used for measurements of weight, length, and bone mineral density and the right for histomorphometrical analysis. The uteri were analyzed with respect to estrogen receptor content. PCB #126 exposure did not affect bone mineral density or trabecular bone volume of tibia in sham-operated rats. In ovariectomized rats PCB #126 exposure resulted in a decreased length and an increased bone mineral density of tibia. An obvious PCB #126 induced increase in osteoid surface was observed in sham-operated rats. The cortical thickness and the organic content of the tibia were also increased in these rats. In estrogen deprived tissue like the uteri of ovariectomized rats, PCB #126 showed weak estrogen agonistic activity. The observed effects of PCB #126 on bone and uterine tissues differed between ovariectomized and sham-operated rats.

  • 179.
    Lind, Monica
    et al.
    Karolinska Institutet, Institute of Environmental Medicine.
    Eriksen, Erik F
    Lind, Lars
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Örberg, Jan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Sahlin, Lena
    Estrogen supplementation modulates effects of the endocrine disrupting pollutant PCB126 in rat bone and uterus: diverging effects in ovariectomized and intact animals.2004In: Toxicology, ISSN 0300-483X, E-ISSN 1879-3185, Vol. 199, no 2-3, p. 129-136Article in journal (Refereed)
    Abstract [en]

    The aims of the present study are to compare effects of estrogen depletion (OVX) and estradiol (E2) supplementation on the tissue effects of exposure to the endocrine disrupting organochlorine 3,3',4,4',5-pentachlorobiphenyl (PCB126). For this purpose two highly estrogen-dependent tissues, bone and uterus, were studied. Forty rats exposed to PCB126 (ip) for 3 months (total dose 384 microg/kg body weight (bw)) were randomized in to OVX/sham operation or E2 supplementation (ip, 23 microg/kg, 3 days weekly) per vehicle (corn oil) groups in a 2 x 2 factorial design. Sham operated rats were treated with vehicle, PCB or PCB plus E2 (sham, sham + PCB and sham + PCB + E2, n=10 per group) whereas ovariectomized were treated with vehicle, PCB or PCB plus E2(OVX, OVX + PCB and OVX + PCB + E2, n=10 per group). As control groups served OVX or sham, and OVX + E2 (n=10 in each group). In OVX rats PCB126 + E2 treatment increased trabecular bone volume (TBV) (P<0.01), whilst the opposite was found in sham-operated rats (P<0.01). In OVX animals exposed to PCB126, E2 supplementation decreased the uterine weight and increased the uterine ERbeta mRNA level, whilst no difference was found between the PCB126 and PCB126 + E2 exposed groups in the sham-operated animals. In conclusion, estrogen modulates PCB126 induced effects on trabecular bone, as well as several uterine parameters. These results further support an important role of estrogen on the toxic effects of PCB126 on bone and uterus.

  • 180.
    Lind, Monica
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Gustafsson, Magnus
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Hermsen, Sanne A B
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Kyle, Carol E
    Örberg, Jan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Rhind, Stewart M
    Exposure to pastures fertilised with sewage sludge disrupts bone tissue homeostasis in sheep2009In: Science of the Total Environment, ISSN 0048-9697, E-ISSN 1879-1026, Vol. 407, no 7, p. 2200-2208Article in journal (Refereed)
    Abstract [en]

    The femurs of male and female sheep (Ovis aries), aged 18 months, bred on pastures fertilized twice annually with sewage sludge (2.25 tonnes dry matter/ha; Treated; T)) or on pastures treated with inorganic fertilizer (Control; C) were studied, using peripheral Quantitative Computed Tomography (pQCT) and the three-point bending test. Males were maintained on the respective treatments from conception to weaning and then maintained on control pastures while the females were maintained on the respective treatments until slaughter. T rams exhibited increased total bone mineral density (BMD) at the metaphyseal part of femur (+10.5%, p<0.01) compared with C rams but had a reduced total cross sectional area (CSA, -11.5%, p<0.001), trabecular CSA (-17.1%, p<0.01) and periosteal circumference (-5.7%, p<0.001). In the mid-diaphyseal part, T rams had an increased total BMD (+13.8%, p<0.0001) and stiffness (+6.4%, p<0.01) but reduced total CSA (-12.1%, p<0.0001) and marrow cavity (-25.8%, p<0.0001), relative to C rams. In ewes although pQCT analysis of neither the metaphyseal nor the mid-diaphyseal part of the female femur bones showed any significant differences with treatment, the biomechanical method revealed a reduction in load at failure (-17.3%, p<0.01) and stiffness (-10.7%, p<0.05) amongst T ewes. It is concluded that exposure to pollutants present in sewage sludge can perturb bone tissue homeostasis in sheep, but particularly in males.

  • 181.
    Lind, Monica
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolutionary Biology.
    Larsson, S
    Johansson, S
    Melhus, H
    Wikström, M
    Lindhe, Ö
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Örberg, J
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Bone tissue composition, dimensions and strength in female rats given an increased dietary level of vitamin A or exposed to 3,3',4, 4',5-pentachlorobiphenyl (PCB126) alone or in combination with vitamin C.2000In: Toxicology, ISSN 0300-483X, E-ISSN 1879-3185, Vol. 151, no 1-3, p. 11-23Article in journal (Refereed)
    Abstract [en]

    In previous studies we have described structural and functional changes in rat bone tissue caused by 3,3',4,4',5-pentachlorobiphenyl (PCB126). Some of the effects caused by PCB126 resemble those found in vitamin C-deficient rats, as well as those found in rats with a high dietary intake of vitamin A. The present investigation was designed to determine if these PCB126-induced changes could be inhibited by addition of vitamin C to the drinking water and if they could be evoked by vitamin A administration. Five groups of female rats were used in this study, which lasted for 12 weeks. Three of the groups were exposed to PCB126 (total dose 320 microgram/kg, bw), either alone or in combination with vitamin C added to the drinking water (1 and 10 g/l, respectively). One group was given feed with increased level of vitamin A (600000 U/kg pellet) and the fifth group served as controls. Using peripheral quantitative computed tomography (pQCT), it was found that PCB126 increased trabecular density and cortical thickness, but reduced the trabecular area. Furthermore, maximum torque and stiffness of the humerus during torsional testing and serum osteocalcin levels were reduced by PCB126. Of the PCB126 induced effects observed, addition of vitamin C only inhibited the reduction of serum osteocalcin. Like PCB126 vitamin A supplementation increased the inorganic content and the bone density and also reduced the trabecular area and polar moment of inertia but did not increase the cortical thickness or reduce maximum torque, stiffness or serum osteocalcin level. Apparently, the effects induced by PCB126 are not mediated either via decreased vitamin C level or increased vitamin A level.

  • 182.
    Lind, Monica
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolutionary Biology.
    Larsson, S
    Oxlund, H
    Håkansson, H
    Nyberg, K
    Eklund, T
    Örberg, J
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Change of bone tissue composition and impaired bone strength in rats exposed to 3,3',4,4',5-pentachlorobiphenyl (PCB126)2000In: Toxicology, ISSN 0300-483X, E-ISSN 1879-3185, Vol. 150, no 1-3, p. 41-51Article in journal (Refereed)
    Abstract [en]

    In previous studies we have described structural and functional changes in rat bone tissue caused by 3,3′,4,4′,5-pentachlorobiphenyl (PCB126). Some of the effects caused by PCB126 resemble those found in vitamin C-deficient rats, as well as those found in rats with a high dietary intake of vitamin A. The present investigation was designed to determine if these PCB126-induced changes could be inhibited by addition of vitamin C to the drinking water and if they could be evoked by vitamin A administration. Five groups of female rats were used in this study, which lasted for 12 weeks. Three of the groups were exposed to PCB126 (total dose 320 μg/kg, bw), either alone or in combination with vitamin C added to the drinking water (1 and 10 g/l, respectively). One group was given feed with increased level of vitamin A (600 000 U/kg pellet) and the fifth group served as controls. Using peripheral quantitative computed tomography (pQCT), it was found that PCB126 increased trabecular density and cortical thickness, but reduced the trabecular area. Furthermore, maximum torque and stiffness of the humerus during torsional testing and serum osteocalcin levels were reduced by PCB126. Of the PCB126 induced effects observed, addition of vitamin C only inhibited the reduction of serum osteocalcin. Like PCB126 vitamin A supplementation increased the inorganic content and the bone density and also reduced the trabecular area and polar moment of inertia but did not increase the cortical thickness or reduce maximum torque, stiffness or serum osteocalcin level. Apparently, the effects induced by PCB126 are not mediated either via decreased vitamin C level or increased vitamin A level.

  • 183.
    Lind, Monica
    et al.
    National Institute of Environmental Medicine, Karolinska Institutet.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Larsson, S
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Örberg, Jan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Torsional testing and peripheral quantitative computed tomography in rat humerus2001In: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 29, no 3, p. 265-270Article in journal (Refereed)
    Abstract [en]

    Peripheral quantitative computed tomography (pQCT) is a noninvasive method mainly used to evaluate the densitometric and geometric properties of bone. In the present study, we evaluate the different variables provided by pQCT examination and their ability to predict the mechanical strength properties of the rat humerus. Humeri from 68 female rats were utilized. These humeri represented bone with a wide range of mechanical and densitometric properties as well as geometric dimensions. Various characteristics, such as volumetric cortical density, total mineral content, cortical thickness, total cross-sectional area, cortical area, and polar strength strain index (SSI), were measured by pQCT. The reproducibility of these measurements was good, with a coefficient of variation (CV) ranging from 0.8% to 4.9%. Bone composition (e.g., ash weight, water content, and inorganic content) and bone dimensions (e.g., length, waist, and volume) were also determined. The mechanical properties (maximum torque, torsion at failure, and stiffness) were measured by torsional testing. Stepwise multiple linear regression was performed to identify the best explanatory variables for each mechanical parameter. Total cross-sectional area and polar SSI were equally well correlated to stiffness (r = 0.57, p < 0.001), whereas ash weight was superior to the pQCT variables to explain maximum torque (r = 0.42, p < 0.001). No other independent pQCT variable entered the two models in the stepwise regression analysis. It was found to be feasible to measure properties of the rat humerus with pQCT. Cross-sectional area and the polar SSI were shown to be the best explanatory variables for stiffness, whereas ash weight was the best predictor for maximum torque.

  • 184.
    Lind, Monica
    et al.
    Institute of Environmental Medicine, Karolinska Institutet.
    Milnes, Matthew R
    Lundberg, Rebecca
    Bermudez, Dieldrich
    Orberg, Jan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Guillette, Louis J
    Abnormal bone composition in female juvenile American alligators from a pesticide-polluted lake (Lake Apopka, Florida)2004In: Journal of Environmental Health Perspectives, ISSN 0091-6765, E-ISSN 1552-9924, Vol. 112, no 3, p. 359-362Article in journal (Refereed)
    Abstract [en]

    Reproductive disorders have been found in pesticide-exposed alligators living in Lake Apopka, Florida (USA). These disorders have been hypothesized to be caused by exposure to endocrine- disruptive estrogen-like contaminants. The aim of this study was to expand our analysis beyond previous studies by investigating whether bone tissue, known to be affected by sex steroid hormones, is a potential target of endocrine disruptors. Long bones from 16 juvenile female alligators from Lake Apopka (pesticide-contaminated lake) and Lake Woodruff (control lake) were evaluated by peripheral quantitative computed tomography. We observed significant differences in bone composition, with female alligators from the contaminated lake having greater trabecular bone mineral density (BMD), total BMD, and trabecular mineral content compared with females from the control lake (p < 0.05). Increased trabecular and total BMD measurements suggest that juvenile female alligators from Lake Apopka were exposed to contaminants that created an internal environment more estrogenic than that normally observed. This estrogenic environment could be caused by both natural and anthropogenic compounds. Effects on BMD indicate interference with bone homeostasis. We hypothesize that contaminants present in the lake inhibit the natural and continuous resorption of bone tissue, resulting in increased bone mass. Although this is the only study performed to date examining effects of environmental estrogenic compounds on alligator bones, it supports previous laboratory-based studies in rodents. Further, this study is important in demonstrating that the alterations in morphology and physiology induced in free-ranging individuals living in environments contaminated with endocrine-active compounds are not limited to a few systems or tissues; rather, effects can be observed in many tissues affected by these hormones.