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Cytochrome P450 1A, 1B, and 1C mRNA induction patterns in three-spined stickleback exposed to a transient and a persistent inducer
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental Toxicology.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental Toxicology.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental Toxicology.
2011 (English)In: Comparative Biochemistry and Physiology - Part C: Toxicology & Pharmacology, ISSN 1532-0456, E-ISSN 1878-1659, Vol. 154, no 1, 42-55 p.Article in journal (Refereed) Published
Abstract [en]

Cytochrome P450 1 (CYP1) mRNA induction patterns in three-spined stickleback (Gasterosteus aculeatus) were explored for use in environmental monitoring of aryl hydrocarbon receptor (AHR) agonists. The cDNAs of stickleback CYP1A, CYP1B1, CYP1C1, and CYP1C2 were cloned and their basal and induced expression patterns were determined in the brain, gill, liver and kidney. Also, their induction time courses were compared after waterborne exposure to a transient (indigo) or a persistent (3,3',4,4',5-pentacholorbiphenyl PCB 126) AHR agonist. The cloned stickleback CYP1s exhibited a high amino acid sequence identity compared with their zebrafish orthologs and their constitutive tissue distribution patterns largely agreed with those reported in other species. PCB 126 (100 nM) induced different CYP1 expression patterns in the four tissues, suggesting tissue-specific regulation. Both indigo (1 nM) and PCB 126 (10 nM) induced a strong CYP1 expression in gills. However, while PCB 126 gave rise to a high and persistent induction in gills and liver, induction by indigo was transient in both organs. The number of putative dioxin response elements found in each CYP1 gene promoter roughly reflected the induction levels of the genes. The high responsiveness of CYP1A,CYP1B1, and CYP1C1 observed in several organs suggests that three-spined stickleback is suitable for monitoring of pollution with AHR agonists.

Place, publisher, year, edition, pages
2011. Vol. 154, no 1, 42-55 p.
Keyword [en]
Three-spined stickleback, Cytochrome P450 1A, Cytochrome P450 1B, Cytochrome P450 1C, CYP1A gene, CYP1B gene, CYP1C gene, Gill EROD activity, Indigo, PCB 126, Biomarkers
National Category
Natural Sciences
Identifiers
URN: urn:nbn:se:uu:diva-155388DOI: 10.1016/j.cbpc.2011.02.005ISI: 000291178700007OAI: oai:DiVA.org:uu-155388DiVA: diva2:426030
Available from: 2011-06-22 Created: 2011-06-22 Last updated: 2017-12-11Bibliographically approved
In thesis
1. Basal and Pollutant-induced Expression of CYP1A, 1B and 1C isoforms in Fish: Implications for Biomonitoring
Open this publication in new window or tab >>Basal and Pollutant-induced Expression of CYP1A, 1B and 1C isoforms in Fish: Implications for Biomonitoring
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Aquatic wildlife are exposed to contaminants in their natural habitats, and toxic pollutants may induce toxicity in sensitive target tissues and cells. There is therefore a need to establish biomarkers to determine exposure to certain classes of contaminants and the subsequent biological responses. In the present work the whole suite of cytochrome P450 1 (CYP1) genes expressed in fish were examined with regard to their inducibility and potential use as biomarkers. Complementary DNA of the CYP1A, 1B and 1C transcripts in rainbow trout and three-spined stickleback were cloned and characterized by quantitative mRNA expression analysis. All CYP1 transcripts could be induced by two selected aryl hydrocarbon receptor (AhR) agoinsts (indigo and PCB 126) in both species, suggesting that all genes were regulated by the AhR. CYP1 mRNA expression profiles induced by PCB 126 and indigo varied over time showing that PCB 126 gave rise to a high and persistent induction in gills and liver while induction by indigo was transient in both organs. The uptake and kinetics of 14C-indigo was studied by autoradiography in rainbow trout. A rapid uptake of 14C-indigo from the water and a subsequent elimination in bile and intestinal contents was observed, explaining the transient CYP1 induction. A high accumulation of 14C-indigo in the gills was completely blocked the CYP1 inhibitor ellipticine, suggesting a CYP1-dependent uptake. High dilutions of a sewage treatment plant effluent containing a complex mixture of pharmaceuticals were investigated. The same water sample both induced CYP1A mRNA expression and inhibited catalytic activity of CYP1A. A field study revealed different induction signatures of the CYP1 genes examined at various locations in Uppsala water environments. As concluded by the temporal and spatial responses obtained, the results of this work suggest that the CYP1 gene panel could be used for biomonitoring of environmental contaminants acting on the CYP system. Further field studies will be required to evaluate this possibility.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2013. 52 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 1044
National Category
Other Biological Topics
Identifiers
urn:nbn:se:uu:diva-198658 (URN)978-91-554-8670-9 (ISBN)
Public defence
2013-05-28, Lindahlsalen, Norbyvägen 18A, Uppsala, 09:15 (English)
Supervisors
Available from: 2013-05-06 Created: 2013-04-22 Last updated: 2013-08-30Bibliographically approved

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