A model system for studying chemical carcinogenesis in colon has been developed. Human colon can generally be maintained 14 days and rat colon at least 63 days as explant cultures. Cultured human and rat colon have the ability to enzymatically convert various classes of chemical carcinogens, such as polycyclic aromatic hydrocarbons, N-nitrosamines, mycotoxins, protein pyrolysis products and hydrazines, into metabolites which react with cellular macromolecules, such as DNA and protein. A wide variation among people in the binding of both benzo(a)pyrene (BP) and 1,2-dimethylhydrazine (DMH) was seen. The data showed a skewed distribtion that strongly suggested a distribution more complex than uni-modality. A positive correlation in the binding of BP to DNA was seen between colon and duodenum from the same individual, the binding level being highest in the duodenum. The carcinogen-DNA adducts for aflatoxin b1 (AFB), BP, N-nitrosodimethylamine and DMH have been identified and the persistence of the AFB-DNA modification have been studied in human colon. The effects of varius suspected inhibitors and enhancers of colon carcinogenesis have been investigated on the metabolism of BP and DMH.