In vitro inhibition of the metabolism and mutagenicity of benzo(a)pyrene and benzo(a)pyrene-7,8-dihydrodiol by naphthazarin and other naphthol derivatives.
Among naphthol derivatives tested in the Ames assay, 5,8-dihydroxy-1,4-naphthoquinone or naphthazarin was found to be the most effective inhibitor of benzo(a)pyrene mutagenicity. The inhibitory activity is due in part to the redox cycling of naphthazarin with the concommitant transfer of reducing equivalents from NADPH to molecular oxygen, thus diverting electrons from cytochrome P-450 enzymes. Metabolite separations showed a decrease in microsomal metabolism of benzo(a)pyrene and of benzo(a)pyrene-7,8-dihydrodoil upon addition of naphthazarin. Since both NADP and dicoumarol inhibited the naphthazarin-stimulated non-stoichiometric consumption of NADPH and oxygen then naphthazarin redox cycling probably involves both DT-diaphorase and NADPH cytochrome P-450 reductase.
D001564:Benzo(a)pyrene / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000633:toxicity; D001728:Dicumarol / Q000494:pharmacology; D004101:Dihydroxydihydrobenzopyrenes / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000633:toxicity; D008861:Microsomes / Q000378:metabolism; D009152:Mutagenicity Tests; D009153:Mutagens; D016660:NAD(P)H Dehydrogenase (Quinone); D009249:NADP / Q000378:metabolism; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D009284:Naphthols / Q000494:pharmacology*; D009285:Naphthoquinones / Q000494:pharmacology*; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000187:drug effects; D011808:Quinone Reductases / Q000378:metabolism
D004101:Dihydroxydihydrobenzopyrenes; D009153:Mutagens; D009284:Naphthols; D009285:Naphthoquinones; C017228:benzo(a)pyrene 7,8-dihydrodiol; D001564:Benzo(a)pyrene; C005503:naphthazarin; D009249:NADP; D001728:Dicumarol; D009251:NADPH-Ferrihemoprotein Reductase; D016660:NAD(P)H Dehydrogenase (Quinone); D011808:Quinone Reductases