Modulatory effects of capsaicin on n-diethylnitrosamine (DEN)-induced mutagenesis in salmonella typhimurium YG7108 and DEN-induced hepatocarcinogenesis in gpt delta transgenic rats

Abstract

Capsaicin from the red chili pepper is a prospective chemopreventive agent. To explore the possible antigenotoxic effects of capsaicin on N-diethylnitrosamine (DEN)- induced mutagenesis in vitro , we conducted bacterial mutation assays with Salmonella typhimurium YG7108, a sensitive strain to mutagenic alkylating agents. Capsaicin was not mutagenic either with or without S9 activation. Unexpectedly,it enhanced the mutagenicity of DEN in the presence of S9 activation significantly. Capsaicin also enhanced the mutagenicity of 2-aminoanthracene and benzo[ a]pyrene in the presence of S9 activation and benzo[ a]pyrene diolepoxide in the absence of S9 activation. However, it reduced the mutagenicity of ethylnitrosourea in the absence of S9 activation. To examine whether capsaicin modulates DEN-induced mutagenesis and hepatocarcinogenesisin vivo,we took advantage ofgpt delta rats, transgenic rodents that carry reporter genes formutations. Femalegpt delta rats were given drinking water containing 40 ppm DEN for five weeks. They were fed diets containing capsaicin at doses of 0, 100 or 500 ppm for seven weeks, starting one week before the DEN treatment. Samples were collected at weeks 7 and 32, respectively, for mutagenicity and carcinogenicity assays. DEN enhanced gpt mutant frequency more than 200 fold in the liver. However, capsaicin displayed no modulating effects on the mutagenesis. Rather, it reduced the number of liver neoplasms, especially liver cell adenomas, in a dosedependent manner although the reduction in hepatocellular carcinoma was statistically insignificant. These results suggest that chemopreventive effect of capsaicin against DEN-induced hepatocarcinogenesis is slight and that the effect is not due to antimutagenesis. The results also caution that chemopreventive effects of chemicals should be examined not only in vitro but alsoin vivo with multiple indexes, e.g., in vitro and in vivo mutations and pathological examinations. © The Japanese Environmental Mutagen Society.