Inhibition of hepatic aryl hydrocarbon hydroxylase by 3-methylcholanthrene, 7,8-benzoflavone and other inducers added in vitro.
A close correlation has been observed between the ability of aromatic polycyclic hydrocarbons and 7,8-benzoflavone (7,8-BF) to induce hepatic aryl hydrocarbon hydroxylase (AHH) in vivo and to inhibit the induced enzyme system in vitro. The activity of this mono-oxygenase was measured by the conversion of 14C-labeled dimethylbenz(a)anthracene (DMBA) or benzo(a)pyrene (BP) to water-soluble products by rat liver preparations (8000 X g supernatant). DMBA as substrate had the advantage over BP in giving a wider range of ethyl acetate-soluble metabolites and allowing the observation of changes in the pattern of these products following injection or addition of the inducing agents. This property was used to detect low concentration (0.1 muM) of polycyclic hydrocarbons which are strong AHH inducers and which may also be carcinogenic. The liver preparation was active for several months when stored at --20 degrees. A possible mechanism of action for the in vitro behaviour of polycyclic hydrocarbons and 7,8-BF towards AHH is proposed.
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors*; D004054:Diethylstilbestrol / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008748:Methylcholanthrene / Q000494:pharmacology*; D011083:Polycyclic Compounds / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship; D013739:Testosterone / Q000494:pharmacology
D005419:Flavonoids; D011083:Polycyclic Compounds; D013739:Testosterone; D004958:Estradiol; D008748:Methylcholanthrene; D004054:Diethylstilbestrol; D001189:Aryl Hydrocarbon Hydroxylases