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Enhanced Induction of Gastric Carcinogenesis by N-Methyl-N'-nitro-N-nitrosoguanidine in Wistar Rats Fed a Low-Protein Diet¹

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

The effects of ad libitum feeding of synthetic, low-protein diets on the incidence and number of gastric cancers induced by N-methyl-N'-nitro-N-nitrosoguanidine were investigated in Wistar rats. Rats were fed synthetic diets of equal calorie content containing 25% casein (normal protein diet), 10% casein (low-protein diet), or 5% casein (very-low-protein diet) after treatment with N-methyl-N'-nitro-N-nitrosoguanidine p.o. for 25 weeks. Administration p.o. of a very-low-protein diet containing 5% casein resulted in a significant increase in the incidence and number of gastric cancers in experimental Week 52. However, it did not affect the histology of the cancers. The very-low-protein diet also caused a significant increase in tissue norepinephrine concentration of the antral portion of the gastric wall and in the labeling index of the antral epithelial cells. These findings indicate that a very-low-protein diet enhances gastric carcinogenesis and that this effect may be related to its effect in increasing norepinephrine in the gastric wall and stimulating proliferation of antral epithelial cells.

¹ This work was supported in part by a grant-in-aid from the Ministry of Health and Welfare, Japan, for a Comprehensive 10-year Strategy for Cancer Control.

² To whom requests for reprints should be addressed.

Received 2/ 5/91. Accepted 4/24/91.