3,2 feet-Dimethyl-4-aminobiphenyl (DMAB) is a powerful arylamine carcinogen which induces colon as well as small intestinal tumors in experimental animals. Although its colon carcinogenicity appears to depend on the transport of metabolites, formed in the liver, via the bile and the fecal stream, and is also influences by the presence or absence of intestinal bacteria, more exact information as to mechanism involved in its organotropism for the colon is not available. This program is intended to clarify the roles of biliary and fecal metabolite transport, the intestinal microflora and the metabolic capacity of the intestinal mucosae in the induction of tumors of the small and large intestine by DMAB in the rat. To this end, the changes which occur in DMAB metabolites from the time of their secretion into the duodenum to the time of their appearance in the colon will be monitored in both germfree and conventional rats, and the ability of the duodenal and colonic mucusae to activate these metabolites or their products will be assayed. Arylamines are widely distributed throughout the environment, and exposure to these agents, several of which have been positively identified as human carcinogens, can stem from dietary as well as industrial sources. Thus clarification of the factors determining the carcinogenicity and organotropism of the model compound DMAB can have important predictive value in assessing the role of this group of chemical in the etiology of human cancer.
