Effects of vitamin C and PCB metabolites on the inhibition of aryl hydrocarbon hydroxylase and suppression of mutagenicity of benzo[ a]pyrene

Abstract

The reverse mutations of Salmonella typhimurium TA98 and TA100 induced by benzo[ a]pyrene (BP) were suppressed by about 90% by vitamin C (1500 μg/plate). Of 11 polychlorinated biphenyl (PCB) metabolites tested (150 μg/plate), 3-methylsulfonyl-3′,4,4′,5-tetrachlorobiphenyl (3-MSF-3′,4,4′,5-tetraCB), 3-MSF-3′,4,4′,5,5′-pentaCB and 4-MSF-3,3′,4′,5,5′-pentaCB also strongly suppressed the mutagenicity of BP. In addition, vitamin C reduced the activity of aryl hydrocarbon hydroxylase (AHH) in microsomes from aromatic hydrocarbon-responsive (Ah-responsive) and Ah-non-responsive strains of mice that had been pretreated with olive oil (vehicle), 3-methylcholanthrene or 2,3,7,8-tetrachlorodibenzo- p-dioxin. Vitamin C affected the AHH activities in the same way in both strains of mice, but the extent of inhibition was somewhat smaller in the Ah-responsive strain than in the Ah-non-responsive strain. In contrast, 3-MSF-3′,4,4′,5-tetraCB, one of the most potent AHH inhibitors among 11 PCB metabolites showed various inhibitory effects depending upon the origin of the microsomes. It is suggested that vitamin C is directly bound to the substrate BP, to cytochrome P-450 itself or to the substrate-enzyme complex, thus lowering the rate of AHH reaction, and that the mechanisms of inhibition of AHH and suppression of mutagenicity by vitamin C are different from those of PCB metabolites.