The effects of cholic acid and bile salt binding agents on 1,2-dimethylhydrazine-induced colon carcinogenesis in the rat

The theory that bile salts may be colon tumour promoters was tested in the dimethylhydrazine (DMH)-induced rat colon cancer model. Fifty Wistar rats were randomly allocated to one of five experimental groups (n = 10), all fed the same standard diet. One group served as saline-injected controls, while the other four groups received DMH (20 mg/kg body weight/rat/week s.c.) for 20 weeks. In addition, each of the DMH-injected groups concurrently received 20 weekly i.g. instillations of one of the following: cholic acid (a bile acid); cholestyramine or aluminium hydroxide (both bile acid binding agents), or water. After a years observation period, all the controls were alive and tumour-free, while all the DMH-injected rats had died of histologically proven colon cancer. Irrespective of the type of gastric instillate, there were no significant differences between the groups in terms of time to tumour presentation, survival, in the necropsy incidence of primary or metastatic colon cancer, or in the numbers of colon tumours per group. The data suggest that bile salts and bile salt binding agents are not colon tumour promoters in the rat. The bile salt theory of colon carcinogenesis may need reappraisal.