[Direct detoxification of N-acetoxy-PhIP by tea polyphenols: a possible mechanism for chemoprevention against PhIP-DNA adduct formation in vivo].
OBJECTIVE
We have shown that green tea inhibited food-borne carcinogen 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP)-induced carcinogen-DNA adduct formation in rats, and this protective effect of tea appears not relote to the modifications of metabolic enzymes involved in PhIP metabolism. The aim of this study was to explore the direct reaction of tea and tea polyphenols with N-acetoxy-PhIP, an ultimate carcinogen of PhIP formed via metabolic activation.


METHODS
DNA binding assays were conducted to examine the effect of aqueous extract of tea and tea polyphenols on the reaction of [3H]N-acetoxy-PhIP with DNA. The reaction mixtures were analyzed by HPLC for the possible product (s) formed by the reaction of [3H]N-acetoxy-PhIP with tea polyphenols.


RESULTS
It was found that agueous extract of tea and tea polyphenols strongly inhibited covalent binding of [3H]N-acetoxy-PhIP to DNA, and the inhibition was concentration-dependent with respect to inhibitors. HPLC analyses of reaction mixture containing [3H]N-acetoxy-PhIP and tea polyphenols revealed the production of the parent amine, PhIP, indicating a redox mechanism.


CONCLUSIONS
In view of the presence of tea polyphenols in rat and human plasma after ingestion of tea, these results suggest that direct reduction of ultimate carcinogen N-acetoxy-PhIP by tea polyphenols is likely to be involved in the mechanism of chemoprevention of tea against PhIP-DNA adduct formation in vivo.
D000818:Animals; D002273:Carcinogens; D018736:DNA Adducts / Q000037:antagonists & inhibitors*; D005419:Flavonoids; D007093:Imidazoles / Q000378:metabolism*; D010636:Phenols / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology; D011108:Polymers / Q000494:pharmacology*; D059808:Polyphenols; D051381:Rats; D013662:Tea / Q000737:chemistry*