Catechin as an antimutagen: its mode of action.

In the present study, we report that the betel quid ingredient catechu, its extract and pure principle catechin were nonmutagenic in Salmonella typhimurium TA 100, TA 1535, TA 98, and TA 1538 assays with or without metabolic activation. They also exhibited dose-dependent decreases in mutagenicity of benzo(a)pyrene [B(a)P] and dimethylbenz(a)anthracene (DMBA) in strain TA 98 with metabolic activation. We further report that these compounds inhibited activities of cytochrome P-450 and had no effect on glutathione-S-transferase but increased the glutathione content in rat liver tissue. Simultaneous treatment of catechin prevented the mutagenic activity of B(a)P and DMBA metabolites in strain TA 98 in the absence of metabolic activation. Pre- and post-treatment of bacteria with catechin had no effect on the mutagenicity of B(a)P and DMBA metabolites. Catechin also inhibited the in vitro binding of 3H-B(a)P metabolites to calf thymus DNA. Catechu extract and catechin inhibited the nitrosation of methylurea by nitrite at pH 3.6 and 30 degrees C. The formation of nitrosomethylurea in the reaction mixture was monitored by measuring the histidine revertants of strain TA 1535 in the absence of metabolic activation. Pre- and post-treatment of catechu extract or catechin had no effect on the mutagenicity of nitrosomethylurea in TA 1535. The nitrosation inhibition by catechin was through scavenging of nitrite observed at pH 3.6. The above study indicates that catechu in betel quid may act as an antimutagen and may suppress the mutagenic potential of other betel quid mutagens.