Cytochrome P450E (P450IA) Induction and Inhibition in Winter Flounder by3,3',4,4'-Tetrachlorobiphenyl: Comparison of Response in Fish from Georges Bank and Narragansett Bay

摘要

Induction of liver microsomal cytochrome P450 by 3,3',4,4'-tetrachlorobiphenyl(TCB) was evaluated in winter flounder from two different sites, one offshore (Georges Bank) and one coastal (Narrow River, Narragansett, Rhode Island). Immunoblot analysis of liver microsomes with monoclonal antibody 1-12-3 to scup P450E (P450IA1) revealed P450IA protein content of 0.01 nmol/mg in Georges Bank fish that were not treated with TCB. By comparison, untreated Narrow River fish had an 80-fold greater content of immunodetected P450IA protein, indicating a strong environmental induction in these fish. In Georges Bank fish the total (spectrophotometrically measured) microsomal P450 content and the content of P450IA protein were induced progressively by intraperitoneal doses of TCB ranging from 0.1 to 10.0 mg/kg. Ethoxyresorufin-O-deethylase (EROD) specific activity (activity per mg protein) was also progressively induced, but the catalytic efficiency or turnover number (i.e., activity/nmol P450IA) was less in fish given the greater doses of TCB. The results show that 3,3',4,4'-TCB induces P450IA in winter flounder and that TCB acts in vivo to inhibit the activity of P450IA enzyme by mechanisms not yet known.