Effects of hydroxy-polychlorinated biphenyl (OH-PCB) congeners on the xenobiotic biotransformation gene expression patterns in primary culture of Atlantic salmon (Salmo salar) hepatocytes.
Hydroxylated metabolites of PCBs [OH-PCBs] represent new health and environmental concern because they have been shown to have agonist or antagonist interactions with hormone receptors (HRs) or hormone-receptor mediated responses. The present study was designed to investigate the estrogenic potency based on anti-AhR signalling effect of three 4-OH substituted PCB congeners (#107, #146 and #187), one 3-OH substituted congener (#138), and the pharmaceutical synthetic estrogen, ethynylestradiol (EE2) in fish in vitro system using primary culture of Atlantic salmon hepatocytes. The effects were studied by quantifying changes in transcripts with gene-sequence primer pairs for a suite of gene responses (AhRalpha, ARNT, CYP1A1, CYP3A, UGT and GST) belonging to the xenobiotic biotransformation system. Our data show that OH-PCB congeners and EE2, decreased AhRalpha and ARNT transcript levels, and CYP1A1, UGT and GST gene expressions, together with CYP3A gene expression. The decreased expression of transcripts for xenobiotic biotransformation system is related to the concentration of individual OH-PCB congener and these responses are typical of reported estrogenic and estrogen-like effects on the CYP system. Modulation of biotransformation pathways by OH-PCBs may alter xenobiotic metabolism leading to the production of toxic reactive molecules, altering pharmacokinetics and diminishing the clearance rate of individual chemicals from the organism.
Mortensen
Anne S
AS
Department of Biology, Norwegian University of Science and Technology (NTNU), Høgskoleringen 5, 7491 Trondheim, Norway.
Braathen
Marte
M
Sandvik
Morten
M
Arukwe
Augustine
A
D000818:Animals; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D001711:Biotransformation / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004967:Estrogens / Q000378:metabolism / Q000633:toxicity*; D004997:Ethinyl Estradiol / Q000633:toxicity; D029941:Fish Proteins / Q000235:genetics / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D014453:Glucuronosyltransferase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D006900:Hydroxylation; D011078:Polychlorinated Biphenyls / Q000378:metabolism / Q000633:toxicity*; D012333:RNA, Messenger / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism; D020317:Salmo salar / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014874:Water Pollutants, Chemical / Q000378:metabolism / Q000633:toxicity*; D015262:Xenobiotics / Q000378:metabolism*
D004967:Estrogens; D029941:Fish Proteins; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D014874:Water Pollutants, Chemical; D015262:Xenobiotics; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D004997:Ethinyl Estradiol; D011078:Polychlorinated Biphenyls; D019363:Cytochrome P-450 CYP1A1; D051544:Cytochrome P-450 CYP3A; D014453:Glucuronosyltransferase; D005982:Glutathione Transferase