Inhibition of PhIP mutagenicity by caffeine, lycopene, daidzein, and genistein.
The heterocyclic amine 2-amino-1-methyl-6-phenylimidazo[4,5-beta]pyridine NPhIP) is a major dietary component in individuals eating cooked meats or fish. This heterocyclic amine requires biochemical activation, mainly through cytochrome P4501A2, and can be detoxified chiefly by 4'hydroxylation through other cytochromes, and be in turn converted through phase 2 enzymes to readily excreted conjugates. The active form of PhIP is mutagenic in Salmonella typhimurium TA98 and is a useful substrate to study the possible chemoprotective action of phytochemicals. We found that black and green tea depressed the mutagenicity of PhIP in dose-related fashion, and decaffeinated tea was less powerful an inhibitor. This led to the study of caffeine, that displayed effective dose-related inhibition of the mutagenicity of PhIP. Other antioxidants such as lycopene, the active antioxidant from tomatoes, and daidzein and genistein from soy products, also had a dose-related inhibition of the mutagenicity of PhIP. We conclude that PhIP is a good substrate found in several human foods to determine the protective effect of phytochemicals from vegetables, and beverages.
Weisburger
J H
JH
American Health Foundation, Valhalla, NY 10595, USA. john_weisburger@nymc.edu
Dolan
L
L
Pittman
B
B
D000975:Antioxidants / Q000494:pharmacology; D001711:Biotransformation; D002110:Caffeine / Q000494:pharmacology*; D002338:Carotenoids / Q000494:pharmacology*; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism; D005504:Food Analysis; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D007093:Imidazoles / Q000037:antagonists & inhibitors* / Q000493:pharmacokinetics / Q000633:toxicity*; D007529:Isoflavones / Q000494:pharmacology*; D000077276:Lycopene; D009152:Mutagenicity Tests; D009153:Mutagens / Q000493:pharmacokinetics / Q000633:toxicity*; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D013662:Tea / Q000737:chemistry
D000975:Antioxidants; D007093:Imidazoles; D007529:Isoflavones; D009153:Mutagens; D013662:Tea; D002338:Carotenoids; D002110:Caffeine; C004742:daidzein; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine; D019833:Genistein; D019388:Cytochrome P-450 CYP1A2; D000077276:Lycopene