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

The effect of dietary cholesterol on azoxymethane (AOM)-inducedcolon carcinogenesis was evaluated with two different sets ofexperiments. Starting at 6 weeks of age, male Donryu rats weredivided into four groups, and fed either control chow or onesupplemented with 1% cholesterol, and with or without AOM (11weekly 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 injectionof AOM. The AOM-treated groups in both experiments developedtumors in the colon and small intestine, whereas no tumors wereseen in the AOM-untreated groups. An interesting observationwas that cholesterol feeding signficantly increased the numberof colon tumors/rat and the number of animals with distant meta-stasesto several organs. Tumor growth and invasiveness were also enhanced,but not significantly. Both bile acids and neutral sterols inthe feces were markedly increased in the rats fed the 1% cholesterolsupplement (2–3 fold and 5–6 fold, respectively).According to these results, it might be postulated that dietarycholesterol revealed potent promoting effects on AOM-inducedcolon carcinogenesis through the mechanism of increasing excretionof bile acids and neutral sterols in the gut.