The permissive role of oxygen-derived free radicals in the development of colonic cancer in the rat. A new theory for carcinogenesis.

The colonic carcinogen 1,2-dimethylhydrazine (DMH) was given to male rats at 10 weeks of age in the form of weekly s.c. injections for 28 weeks. The results obtained show that the incidence of colonic cancer is directly dependent on dietary fat intake and that carcinogens which produce colonic cancer in the presence of a high-fat diet are rendered harmless when a low-fat diet is consumed. These results suggest that dietary fat is permissive for colonic carcinogenesis. Administration of the radical scavengers allopurinol and dimethyl sulfoxide afforded dose-dependent protection against this permissive role.