Modification by five antioxidants of 1,2-dimethylhydrazine-initiated colon carcinogenesis in F344 rats

Abstract

The effects of antioxidants given in the post initiation phase of colon tumor development were investigated in male F344 rats treated with 1,2-dimethylhydrazine (DMH). Animals (20/group) were given s.c. injections of DMH at a dose of 20 mg/kg once a week for four consecutive weeks. One week after the last injection, rats were fed diet containing 5% sodium L-ascorbate (SA), 0.5% butylated hydroxyanisole (BHA), 0.8% ethoxyquin (EQ), 1.0% propyl gallate or 0.5% butylated hydroxytoluene (BHT) for 36 weeks. A control group was fed the basal diet not containing antioxidants. The experiment was terminated 40 weeks after the first injection of DMH and all intestinal tumors were confirmed histologically. SA significantly increased the incidence of adenomas and the number of tumors per rat of the colon (especially of the distal colon). Although EQ and BHT did not affect the number of rats with colon tumors, the number of tumors per rat occurring in the distal colon was significantly increased by EQ while being decreased by BHT. No modification of tumor development was observed with BHA or PG. Thus, modification of tumor development by SA, EQ and BHT was apparent, mainly in the distal colon.