INHIBITION OF PHIP MUTAGENICITY BY CAFFEINE, LYCOPENE, DAIDZEIN, AND GENISTEIN

The heterocyclic amine 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a major dietary component in individuals eating cooked meat s or fish. This heterocyclic amine requires biochemical activation, ma inly through cytochrome P4501A2, and can be detoxified chiefly by 4'-h ydroxylation through other cytochromes, and be in turn converted throu gh phase 2 enzymes to readily excreted conjugates. The active form of PhIP is mutagenic in Salmonella typhimurium TA98 and is a useful subst rate to study the possible chemoprotective action of phytochemicals. W e found that black and green tea depressed the mutagenicity of PhIP in dose-related fashion, and decaffeinated tea was less powerful an inhi bitor. This led to the study of caffeine, that displayed effective dos e-related inhibition of the mutagenicity of PhIP. Other antioxidants s uch as lycopene, the active antioxidant from tomatoes, and daidzein an d genistein from soy products, also had a dose-related inhibition of t he mutagenicity of PhIP. We conclude that PhIP is a good substrate fou nd in several human foods to determine the protective effect of phytoc hemicals from vegetables, fruits and beverages. (C) 1998 Elsevier Scie nce B.V. All rights reserved.