Evaluation of the antimutagenic effect of (-)-epegallocatechin gallate (EGCG) against chemical-induced mutagenesis of transgenic HITEC mice

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The antimutagenic activity of epegallocatechin gallate (EGCG), the major water soluble compound of green tea, against benzo[a]pyrene (B[a]P)-induced mutations were assessed by using transgenic mice carrying rpsL gene as a monitor of somatic mutations (HITEC mice). EGCG has been known to inhibit cytochrome P450. Male mice of 7 weeks old were given drinking water containing EGCG for 3 weeks. On day 7, mice were treated with a single i.p. injection of B[alpha]P (500 mg/kg bwt). Two weeks after the injection the mutaion of rpsL gene were analyzed. B[a]P treatment resulted in the significant approximately 4Ofold increase of mutation frequency in the lung of HITEC mice. Approximately 60% suppression of B[a]P-induced mutations in the lung was observed when mice were given EGCG at concentraions higher than 0.005% EGCG.B[alpha]P-induced mutations mainly occurred at G : C base-pairs. The majority of base substitutions were G : C*C : G transversions, followed by G : C*T : A transversions and G : C*A : T transitions. B[a]P-induced mutations frequently occurred in the several specific nucleotide sequences of the rpsL gene. These were AGC, CGC, CGT, TGC and CGT ; all of them contained guanine residue. B[a]P-induced mutaions seen in the mouse ras codon 12 or human p53 codon 157 were found in the rpsL gene, and that the mutations were suppressed by EGCG for B[alpha]P-induced mutagenesis in vivo suggest that the drinking of tea may reduce the tumor-initiating potency of B[a]P in the lung.