Competition between benzo[a]pyrene and various steroids for cytochrome P-450-dependent rat liver monooxygenases.
Cytochrome P-450-dependent monooxygenases are able to oxidize a large variety of endogenous and exogenous substrates. This paper describes the in vitro interaction between benzopyrene and steroids at the level of two rat liver monooxygenases: steroid-16 alpha-hydroxylase and aryl hydrocarbon hydroxylase (AHH). The results obtained suggest the following conclusions: (1) Steroid-16 alpha-hydroxylase is partially supported by a specific cytochrome P-450 form which is not inhibited in vitro by exogenous substrates. Steroid-16 alpha-hydroxylase is completely independent from cytochrome P1-450 (or P-448), as it is insensitive, in vitro, to alpha-naphthoflavone; (2) AHH is supported by two cytochrome P-450 forms: a specific form which is inducible by methylcholanthrene and inhibited in vitro by alpha-naphthoflavone, but is insensitive to metyrapone and steroids; and another less specific form which is inhibited by metyrapone and steroids in vitro.
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors*; D001571:Benzoflavones / Q000494:pharmacology; D001579:Benzopyrene Hydroxylase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001580:Benzopyrenes / Q000494:pharmacology*; D001667:Binding, Competitive; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D003687:Dehydroepiandrosterone / Q000494:pharmacology; D004790:Enzyme Induction; D005260:Female; D008099:Liver / Q000187:drug effects; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D008797:Metyrapone / Q000494:pharmacology; D008862:Microsomes, Liver / Q000201:enzymology; D010634:Phenobarbital / Q000494:pharmacology; D011280:Pregnanolone / Q000494:pharmacology; D011374:Progesterone / Q000494:pharmacology; D051381:Rats; D039181:Steroid 16-alpha-Hydroxylase; D013250:Steroid Hydroxylases / Q000032:analysis* / Q000378:metabolism; D013256:Steroids / Q000494:pharmacology*; D013379:Substrate Specificity; D013739:Testosterone / Q000494:pharmacology
D001571:Benzoflavones; D001580:Benzopyrenes; D013256:Steroids; D013739:Testosterone; D003687:Dehydroepiandrosterone; D011374:Progesterone; D008748:Methylcholanthrene; C011512:alpha-naphthoflavone; D003577:Cytochrome P-450 Enzyme System; D011280:Pregnanolone; D013250:Steroid Hydroxylases; D001579:Benzopyrene Hydroxylase; D001189:Aryl Hydrocarbon Hydroxylases; D039181:Steroid 16-alpha-Hydroxylase; D010634:Phenobarbital; D008797:Metyrapone