The objective of this project is to characterize transmissible murine colonic hyperplasia (TMCH), a natural disease of mice, as a potential animal model for human large bowel cancer. The etiology has been found to be a specific isolate of Citrobacter freundii, which causes a severe but transient hyperplasia of the distal colonic mucosa. The severity of TMCH is dependent upon the mouse genetic strain and the diet fed. The cell kinetics of TMCH are being analyzed using autoradiography. Data compiled to date reveal a prolongation of the total cell cycle time and S phase, while the G2 phase is shortened. Migration rate is accelerated. Mitotic activity occurs along the entire crypt column, including the surface mucosa. Ultrastructural studies are being performed to correlate with light microscopic and cell kinetic findings. The dietary components responsible for development of TMCH are being sought be feeding trials with semisynthetic diets. The interaction of TMCH with chemical carcinogenesis, using the carcinogen 1,2-dimethylhydrazine (DMH) is being investigated. The hyperplastic stimulus of TMCH has been found to reduce the latent period for appearance of DMH neoplasia and promote neoplasia after single or reduced doses of DMH.