EFFECTS OF COMPOUNDS OF PLANT-ORIGIN ON THE MUTAGENICITY AND METABOLISM OF THE TOBACCO-SPECIFIC NITROSAMINE NNK

We have investigated the effects of five phytochemicals on the microso mal-dependent mutagenicity and metabolism of the tobacco-specific nitr osamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Two com pounds, d-limonene and silymarin, had no effect on NNK-induced mutagen esis in Salmonella typhimurium TA1535 over the concentration range of 0.1-0.4 mu mol/plate. Diallyl sulphide was weakly antimutagenic at a c oncentration of 0.4 mu mol/plate. Both capsaicin and tannic acid showe d a dose-dependent inhibition of mutagenesis in TA1535. Metabolism stu dies using [H-3]NNK indicated that the effects of the phytochemicals a n NNK-induced mutagenesis did not always correlate with the effects on NNK metabolism. alpha-Carbon hydroxylation reactions are considered t he most significant pathways involved in the metabolic activation of N NK to mutagenic and carcinogenic species. D-Limonene and silymarin (0, 4 mu mol) had the least inhibitory effect on the total alpha-carbon hy droxylation reactions, 19% and 28%. Capsaicin and diallyl sulphide inh ibited these pathways by 74% and 70%. Tannic acid, the most potent phy tochemical tested in this study, inhibited total alpha-carbon hydroxyl ation pathways by 99%.