Cancer chemopreventive mechanisms of tea against heterocyclic amine mutagens from cooked meat

Cooking meat and fish under normal conditions produces heterocyclic amine m utagens, several of which have been shown to induce colon tumors in experim ental animals, In our search for natural dietary components that might prot ect against these mutagens, it was found that green tea and black tea inhib it the formation of heterocyclic amine-induced colonic aberrant crypt foci (ACF) in the rat. Since ACF are considered to be putative preneoplastic les ions, we examined the inhibitory mechanisms of tea against the heterocyclic amines. In the initial studies using the Salmonella mutagenicity assay, gr een tea and black tea inhibited according to the concentration of tea leave s during brewing and the time of brewing; a 2-3-min brew of 5% green tea (w /v) was sufficient for >90% antimutagenic activity. N-hydroxylated heterocy clic amines, which are direct-acting mutagens in Salmonella, were inhibited by complete tea beverage and by individual components of tea, such as epig allocatechin-3-gallate (EGCG). Inhibition did not involve enhanced mutagen degradation, end EGCG and other catechins complexed only weakly with the mu tagens, suggesting electrophile scavenging as an alternative mechanism. Enz ymes that contribute to the metabolic activation of heterocyclic amines, na mely microsomal NADPH-cytochrome P450 reductase and N,O-acetyltransferase, were inhibited by tea in vitro. Studies in vivo established that tea also i nduces cytochromes P450 and Phase II enzymes in a manner consistent with th e rapid metabolism and excretion of heterocyclic amines, Collectively, the results indicate that tea possesses anticarcinogenic activity in the colon, and this most likely involves multiple inhibitory mechanisms.