Colon carcinogenesis in germ-free rats with 1,2-dimethylhydrazine and N-methyl-n'-nitro-N-nitrosoguanidine.

Abstract

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.