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 microsomal‐dependent mutagenicity and metabolism of the tobacco‐specific nitrosamine, 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanone (NNK). Two compounds, d‐limonene and silymarin, had no effect on NNK‐induced mutagenesis in Salmonella typhimurium TA1535 over the concentration range of 0.1–0.4 μmol/plate. Diallyl sulphide was weakly antimutagenic at a concentration of 0.4 μmol/plate. Both capsaicin and tannic acid showed a dose‐dependent inhibition of mutagenesis in TA1535. Metabolism studies using [³H]NNK indicated that the effects of the phytochemicals on NNK‐induced mutagenesis did not always correlate with the effects on NNK metabolism. α‐Carbon hydroxylation reactions are considered the most significant pathways involved in the metabolic activation of NNK to mutagenic and carcinogenic species. D‐Limonene and silymarin (0,4 μmol) had the least inhibitory effect on the total α‐carbon hydroxylation reactions, 19% and 28%. Capsaicin and diallyl sulphide inhibited these pathways by 74% and 70%. Tannic acid, the most potent phytochemical tested in this study, inhibited total α‐carbon hydroxylation pathways by 99%.