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Colon Carcinogenesis with Azoxymethane and Dimethylhydrazine in Germ-free Rats¹

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 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% of 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 that the intestinal microbial populations alter the effect of carcinogens in the large intestine.

¹ Supported by USPHS Contract 1-CP-43378, Grants CA-15400 and CA-16382, from the National Cancer Institute.

Received 8/ 1/74. Accepted 10/ 1/74.

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