Inhibition of benzo(a)pyrene monooxygenase by alpha-naphthoflavone may be partially mediated by the metabolite 9-hydroxy-alpha-naphthoflavone

Abstract

alpha-Naphthoflavone (ANF) inhibits beta-naphthoflavone-induced rat liver microsomal benzo(a)pyrene metabolism and is transformed by these microsomes into alpha-naphthoflavone metabolites. We determined the inhibitory effect on benzo(a)pyrene (B(a)P) metabolism of several of these metabolites and of 6-methoxy-ANF, using beta-naphthoflavone-induced rat liver microsomes. 9-Hydroxy-ANF was the most active inhibitor (I50 = 1.47 microM) and was metabolized from ANF by these hepatic microsomes in concentrations which are inhibitory. Therefore, 9-hydroxy-ANF a microsomal metabolite of ANF, may play a role in the inhibition of B(a)P oxidation by ANF.