title: Role of cytochrome P4501A in biotransformation of the potential anticancer drug oracin.
abstract: Metabolic fate of the potential anticancer drug oracin (I), was studied at microsomal level in rat using enzyme induction and inhibition. One of the main metabolites arising during incubation of hepatic microsomal fraction with oracin is 3-hydroxyoracin (III). Cytochromes P450 non-specific inhibitors (carbon monoxide, aminobenzotriazole, 1-benzylimidazole, proadifen hydrochloride, n-octylamine) diminished amount of III. Among several specific inducers of rat cytochromes P450 isoforms used, only 3-methylcholanthrene, inducer of cytochrome P4501A, caused a significant stimulation of 3-hydroxyoracin production. The amount of III was decreased to the level of controls when the microsomes prepared from 3-methylcholanthrene treated rats were incubated with substrate in the presence of specific P4501A inhibitor alpha-naphthoflavone. From the above mentioned results we can assume that metabolite III is formed from oracin by cytochrome P450 belonging to subfamily 1A.
authors.affiliation: Faculty of Pharmacy, Charles University, Hradec Králové, Czech Republic.
authors.forename: B
authors.initials: B
authors.lastname: Szotáková
authors.forename: V
authors.initials: V
authors.lastname: Wsól
authors.forename: L
authors.initials: L
authors.lastname: Skálová
authors.forename: E
authors.initials: E
authors.lastname: Kvasnicková
mesh_terms: D000815:Aniline Hydroxylase / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D001571:Benzoflavones / Q000494:pharmacology; D001711:Biotransformation; D019363:Cytochrome P-450 CYP1A1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D019362:Cytochrome P-450 CYP2B1 / Q000378:metabolism; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004983:Ethanolamines / Q000493:pharmacokinetics*; D007546:Isoquinolines / Q000493:pharmacokinetics*; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D008862:Microsomes, Liver / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000970:Antineoplastic Agents; D001571:Benzoflavones; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D004983:Ethanolamines; D007546:Isoquinolines; C103439:oracine; D008748:Methylcholanthrene; C011512:alpha-naphthoflavone; D003577:Cytochrome P-450 Enzyme System; D000815:Aniline Hydroxylase; D019363:Cytochrome P-450 CYP1A1; D019362:Cytochrome P-450 CYP2B1