Differential sensitivity of Ah-responsive mice to beta-naphthoflavone-induced metabolism and mutagenesis of benzo[a]pyrene and aflatoxin B1.

Abstract

Effects of the administration to C57BL/6ha (Ah-responsive) mice of a low (10 mg/kg) and a high dose (150 mg/kg) of beta-naphthoflavone (BNF) on the hepatic microsome-mediated mutagenesis and metabolism of benzo[a]pyrene (BP) and aflatoxin B1 (AFB1) were studied. Hepatic microsome-mediated mutagenesis of benzo[a]pyrene was not enhanced by the low dose (10 mg/kg) but at the high dose (150 mg/kg) the mutagenic activation was enhanced several fold relative to control (corn oil-treated). Mutagenic activity of aflatoxin B1 was however depressed by both the low and the high doses of beta NF. These results are consistent with the effects of beta NF administration on hepatic microsome-mediated metabolism of BP to its phenolic products and on the metabolism of aflatoxin B1 to aflatoxin M1 catalyzed by aflatoxin B1-4-hydroxylase. Relative to control, pretreatment of the mice with 10 mg/kg beta NF did not induce aryl hydrocarbon hydroxylase activity (a measure of BP metabolism), however, the same pretreatment induced the metabolism of AFB1 to AFM1 by 2.7 to 4.7-fold. Microsomal preparations from 150 mg/kg beta NF-pretreated mice showed a 3-fold induction of aryl hydrocarbon hydroxylase activity and a 6.8-fold induction of AFB1-4-hydroxylase activity. These results suggest that two different enzyme systems are involved in the metabolism of BP and the metabolism of AFB1 to AFM1.