Colon carcinogenesis with azoxymethane and dimethylhydrazine in germ-free rats

Abstract

The effect of intestinal microflora on the sensitivity of the colon to the carcinogenic effect of azoxymethane and a large dose of 1,2-dimethylhydrazine was studied using germ-free and conventional female Fischer rats. Injection s. c. of 1,2-dimethylhydrazine-induced tumors of the ear duct, kidney, and small intestine of conventional rats but none in germ-free animals. Only 20% germ-free rats showed 1,2-dimethylhydrazine-induced colonic tumors, whereas 93% of conventional rats developed multiple colonic tumors. Intrarectal instillation of azoxymethane appreciably increased the multiplicity of colonic tumors in germ-free rats and in gnotobiotic rats contaminated with Clostridium perfringens, as compared to conventional controls. None of the germ-free rats showed ear duct tumors. The incidence of kidney tumors was lower in germ-free rats than in other groups. It is concluded than the intestinal microbial populations alter the effect of carcinogens in the large intestine.