Effect of xenoestrogen exposure on the expression of cytochrome P450 isoforms in rainbow trout liver.
We studied the estrogenic effects of model chemicals in one-year-old juvenile rainbow trout. Methoxychlor (20 mg/kg), diethylstilbestrol (15 mg/kg), 4-tert-octylphenol (25 and 50 mg/kg), and biochanin A (25 and 50 mg/kg) were injected intraperitoneally on days 1, 4, and 7. Fish were sacrificed on day 9 and examined for multiple biomarkers. All of the test chemicals caused increases in plasma vitellogenin levels, a biomarker of estrogenicity. Treatment with the xenoestrogens decreased hepatic lauric acid hydroxylase activity and, as shown by Western blots, also generally reduced expression of hepatic cytochrome P450s 2K1 (CYP2K1), 2M1 (CYP2M1), and 3A27 (CYP3A27) at the protein level. Both doses of biochanin A also significantly induced P4501A (CYPIA) and greatly increased hepatic 7-ethoxyresorufin-O-deethylase (EROD) activity. These findings suggest that methoxychlor, diethylstilbestrol, 4-tert-octylphenol, and biochanin A were all estrogenic and mimicked 17beta-estradiol (E2) in repressing the expression of cytochrome P450 isoforms (CYP2KI, CYP2M1, and CYP3A27) in the rainbow trout liver. Additionally, biochanin A was found to induce CYPIA in this fish species.
Katchamart
Sirinmas
S
Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis 97331, USA.
Miranda
Cristobal L
CL
Henderson
Marilyn C
MC
Pereira
Clifford B
CB
Buhler
Donald R
DR
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D042926:Cytochrome P-450 CYP4A; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004054:Diethylstilbestrol / Q000494:pharmacology; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D019833:Genistein / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D007527:Isoenzymes; D008297:Male; D008731:Methoxychlor / Q000494:pharmacology; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors; D017686:Oncorhynchus mykiss / Q000378:metabolism*; D010636:Phenols / Q000494:pharmacology; D014819:Vitellogenins / Q000097:blood; D014874:Water Pollutants, Chemical / Q000494:pharmacology*
D065607:Cytochrome P-450 Enzyme Inhibitors; D007527:Isoenzymes; D010636:Phenols; D014819:Vitellogenins; D014874:Water Pollutants, Chemical; D004958:Estradiol; D004054:Diethylstilbestrol; D003577:Cytochrome P-450 Enzyme System; D019833:Genistein; D006899:Mixed Function Oxygenases; D042926:Cytochrome P-450 CYP4A; C105260:4-tert-octylphenol; D008731:Methoxychlor; C004541:biochanin A