Role of cytochrome P4501A in biotransformation of the potential anticancerdrug oracin

Metabolic fate of the potential anticancer drug oracin (I), was studied at microsomal level in rat using enzyme induction and inhibition. One of the m ain metabolites arising during incubation of hepatic microsomal fraction wi th oracin is 3-hydroxyoracin (III). Cytochromes P450 non-specific inhibitor s (carbon monoxide, aminobenzotriazole, l-benzylimidazole, proadifen hydroc hloride, n-octylamine) diminished amount of III. Among several specific ind ucers of rat cytochromes P450 isoforms used, only 3-methylcholanthrene, ind ucer of cytochrome P4501A, caused a significant stimulation of 3-hydroxyora cin production. The amount of III was decreased to the level of controls wh en the microsomes prepared from 3-methylcholanthrene treated rats were incu bated with substrate in the presence of specific P4501A inhibitor a-naphtho flavone. From the above mentioned results we can assume that metabolite III is formed from oracin by cytochrome P450 belonging to Subfamily 1A.