The correlation between cholecystectomy and fecal bile acids, and large-bowel cancer induced with 1,2-dimethylhydrazine in mice

Abstract

The relationship between cholecystectomy and large-bowel cancer development was investigated in animal models. Female ICR mice underwent cholecystectomy, and received 15 weekly intragastric administrations (Experiment 1) or 10 weekly subcutaneous injections (Experiment 2) of 15 mg/kg body weight of large-bowel carcinogen 1,2-dimethylhydrazine (DMH). Autopsy at 28 weeks after surgery showed that cholecystectomized mice had a nonsignificantly increased incidence of large-bowel carcinomas, compared to sham-operated and/or unoperated control mice (85 vs. 64 percent in Experiment 1; 31 vs. 16 and 20 percent in Experiment 2). Cholecystectomy alone without DMH treatment did not produce any cancer. Cholecystectomized mice excreted a significantly increased level of primary bile acids but an unchanged level of secondary bile acids in the feces, compared with unoperated control mice. It is obvious that cholecystectomy enhanced the development of DMH-induced, large-bowel carcinomas along with the change of fecal bile acid composition, suggesting that changes of bile acid metabolism after cholecystectomy may enhance or promote large-bowel carcinogenesis in man as well. This association of cholecystectomy and large-bowel cancer is not a strong one, however, as presented in epidemiologic as well as experimental studies.

Large Bowel Cancer Risk in Cholelithiasis and after Cholecystectomy

“…The finding of an increased tumor yield in mice [45] (70% after CE compared with 16% in controls) was not confirmed by a subsequent study [46]. A more recent animal study [47] looked at the effect of CE on large bowel can cer development and on bile acid metabo lism simultaneously. The number of tumor bearing animals and the number of tumors increased, but not significantly; total bile acid excretion in feces was increased, how ever mainly due to primary bile acids.…”