Effect of calcium on the formation of colonic pre-neoplastic lesions induced by azoxymethane and hemin in mice

Red meats are important animal foods because of their nutritional aspects, but the over-consumption of red meat produces reactive oxygen species (ROS) caused by heme iron and induces colorectal cancer. The effect of orally administered hemin and calcium provided in drinking water for 6 weeks on colon carcinogenesis was observed in male ICR mice. After the mice were acclimated for 1 week, they received three subcutaneous azoxymethane (AOM, 10 mg/kg b.w.) injections weekly and were provided with 2% dextran sodium sulfate (DSS) via drinking water for the next week. The mice were divided into three groups: the control, hemin, and hemin + calcium groups. The orally administered daily dose of hemin was 2 g/kg b.w., and 0.05% calcium was provided daily via drinking water. Colonic mucosa samples were stained with methylene blue, and then, the numbers of aberrant crypt (AC) and aberrant crypt foci (ACF) were counted. Lipid peroxidation in feces was estimated by thiobarbituric acid-reactive substances (TBARS) assay. The total numbers of AC and ACF per colon in the hemin group were significantly higher than those in the control group. Calcium treatment significantly decreased the numbers of ACF and AC in the colon of mice. The TBARS value in the feces of the hemin + calcium group was significantly lower than that in the feces of the hemin group. These results showed that hemin enhances the formation of pre-neoplastic lesions in the colon of mice and that calcium decreases the risk of colon carcinogenesis.