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Inhibition of N-Methyl-N'-nitro-N-nitrosoguanidine-induced Carcinogenesis by (-)-Epigallocatechin Gallate in the Rat Glandular Stomach¹

First Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto 602 [T. Y., T. T., K. K., K. O., M. I., Y. K.], and Research Institute, Saitama Cancer Center Institute, Saitama 358, [M. S., H. F.], Japan

Recently, an epidemiological study showed a lower risk of gastric cancer among people who consume a large amount of green tea. (-)-Epigallocatechin gallate (EGCG), one of the main constituents of green tea, inhibited tumor promotion by teleocidin in a two-stage carcinogenesis experiment with the use of mouse skin.

The inhibitory effect of EGCG on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced carcinogenesis of the glandular stomach in rats was examined. The percentage of tumor-bearing rats in the group treated with MNNG plus EGCG was 31%, compared to 62% in the MNNG group. The difference was statistically significant (P < 0.05).

To assess the effect of p.o. administration of EGCG, the gastric mucosal cellular kinetics was examined with the use of the bromodeoxyuridine labeling index, ornithine decarboxylase activity, and tissue polyamine levels. The labeling index of the EGCG treatment group decreased significantly (P < 0.05) compared to the EGCG plus MNNG treatment group. The ornithine decarboxylase activity and tissue spermidine levels were also decreased. On the other hand, the tissue putrescine and spermine levels were partly increased. These findings suggest that EGCG inhibits the cellular kinetics of the gastric mucosa during the promotion stage of MNNG-induced gastric carcinogenesis. EGCG may be useful in preventing gastric carcinogenesis. Moreover, EGCG may be applied clinically without any harmful effects and at a low cost.

¹ This work was supported by Grants-in-Aid for Cancer Research from the Ministry of Health and Welfare of Japan.

² To whom requests for reprints should be addressed.

Received 11/29/94. Accepted 3/ 9/95.

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