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Effect of Cimetidine on Inhibition by Tetragastrin of Carcinogenesis Induced by N-Methyl-N'-nitro-N-nitrosoguanidine in Wistar Rats

Departments of Gastrointestinal Oncology [M. T., H. I., H. Y., M. B., R. Y.] and Pathology [H. T.], The Center for Adult Diseases, Osaka, 3-3, Nakamichi 1-chome, Higashinari-ku, Osaka 537, Japan

The effects of combined administration of cimetidine and tetragastrin on gastric acid secretion, the labeling index of the gastric mucosa, and the incidence of gastric adenocarcinomas induced by N-methyl-N'-nitro-N-nitrosoguanidine were investigated in inbred Wistar rats. Prolonged administration of tetragastrin in depot form after treatment with N-methyl-N'-nitro-N-nitrosoguanidine resulted in a significant increase in gastric acid secretion, a significant decrease in the labeling index of the antral mucosa, and a significant decrease in the incidence of adenocarcinomas of the glandular stomach. Administration of cimetidine at 20 mg, but not 10 mg, per kg body weight with tetragastrin significantly reduced the gastric acid secretion induced by tetragastrin alone but did not influence the labeling index of the antral mucosa or the inhibitory effect of tetragastrin on gastric carcinogenesis. These findings indicate that gastric acid secretion has no influence on the development of gastric adenocarcinomas and that the inhibitory effect of tetragastrin on gastric carcinogenesis may be related to its effect in decreasing proliferation of cells in the antral mucosa.

¹ To whom requests for reprints should be addressed.

Received 7/30/87. Revised 11/17/87. Accepted 12/ 3/87.

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