Carcinogenesis, Vol. 20, No. 3, 421-424,
March 1999
© 1999 Oxford University Press
Inhibition of benzo[a]pyrene-induced mutagenesis by (–)-epigallocatechin gallate in the lung of rpsL transgenic mice
Laboratory of Drug Metabolism, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812,
1 Institute of Medical Sciences, Tokai University, Isehara 259-1100,
2 Institute of Medical Sciences, University of Tokyo, Bunkyo-ku, Tokyo 113-0033 and
3 Division of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-0054, Japan
Epigallocatechin gallate (EGCG) is a major water-soluble component of green tea. The antimutagenic activity of EGCG against benzo[a]pyrene (B[a]P)-induced mutations was assessed by using transgenic mice carrying the rpsL gene as a monitor of mutations. Seven-week-old male mice were given drinking water containing EGCG for 3 weeks. On day 7, mice were treated with a single i.p. injection of B[a]P (500 mg/kg body wt). Two weeks after the injection, the mutations in the rpsL gene were analyzed. B[a]P treatment resulted in an ~4-fold increase of mutation frequency at the rpsL gene in the lung. An ~60% reduction in the B[a]P-induced mutations in the lung was observed when mice were given EGCG at concentrations >0.005%. B[a]P-induced mutations mainly occurred at G:C base-pairs in the several specific nucleotide sequences of the rpsL gene. These were AGG, CGG, CGT, TGG, TGC and GGT: all of them contained a guanine residue. Mutations seen similarly in the human Ki-ras codon 12 or p53 codons 157, 248, and 273 of lung tumor were also found in the rpsL gene, and the mutations were suppressed by the EGCG treatment. In conclusion, the antimutagenic effects of EGCG for B[a]P-induced mutagenesis in vivo suggest that drinking green tea may reduce the tumor-initiating potency of B[a]P in the lung.
Abbreviations: AFB1, aflatoxin B1; B[a]P, benzo[a]pyrene; BPDE, (±)-7ß,8
-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene; EGCG, (–)-epigallocatechin gallate; KM, kanamycin; SM, streptomycin.
4 To whom correspondence should be addressed Email: kamataki{at}pharm.hokudai.ac.jp
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