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Colon Carcinogenesis in Germ-free Rats with 1,2-Dimethylhydrazine and N-Methyl-N'-nitro-N-nitrosoguanidine¹

Divisions of Nutrition and Experimental Pathology, The Naylor Dana Institute for Disease Prevention, American Health Foundation, New York, New York 10021

The effect of intestinal microflora on the sensitivity of the colon to the carcinogenic effect of 1,2-dimethylhydrazine (DMH), which needs metabolic activation, and N-methyl-N'-nitro-N-nitrosoguanidine a direct-acting carcinogen, was studied using Fischer germ-free and conventional female rats. None of the germ-free rats that received s.c. injections of DMH, 10 mg/week/kg body weight for 20 weeks and autopsied after the last injection showed colon tumors, whereas 17% of the conventional rats treated similarly developed adenocarcinomas of the colon. At 20 weeks after the last injection of DMH, 11% of germ-free rats developed adenomas, whereas 25% of the conventional rats showed colonic tumors, 67% of which were adenocarcinomas and 34% of which were adenomas. In contrast to DMH, i.r. injection of N-methyl-N'-nitro-N-nitrosoguanidine (total dose, 48 mg in 20 weeks) nearly doubled the multiple colonic tumors in germ-free rats compared to conventional controls. It is concluded that the intestinal microflora play a modifying role in colon carcinogenesis by DMH.

¹ Supported by USPHS Contract NO 1-CP-43378 and Grant CA-15400 from the National Cancer Institute.

Received 3/20/74. Accepted 6/ 4/74.

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