Effect of dietary cholesterol on azoxymethane-induced colon carcinogenesis in rats

The effect of dietary cholesterol on azoxymethane (AOM)-induced colon carcinogenesis was evaluated with two different sets of experiments. Starting at 6 weeks of age, male Donryu rats were divided into four groups, and fed either control chow or one supplemented with 1% cholesterol, and with or without AOM (11 weekly s.c. injections at a dosage of 7.4 mg/kg body weight). The rats were sacrificed at 20 weeks after (first experiment) and at 15 weeks after (second experiment) the last injection of AOM. The AOM-treated groups in both experiments developed tumors in the colon and small intestine, whereas no tumors were seen in the AOM-untreated groups. An interesting observation was that cholesterol feeding significantly increased the number of colon tumors/rat and the number of animals with distant metastases to several organs. Tumor growth and invasiveness were also enhanced, but not significantly. Both bile acids and neutral sterols in the feces were markedly increased in the rats fed the 1% cholesterol supplement (2-3 fold and 5-6 fold, respectively). According to these results, it might be postulated that dietary cholesterol revealed potent promoting effects on AOM-induced colon carcinogenesis through the mechanism of increasing excretion of bile acids and neutral sterols in the gut.