Effect of dietary calcium on colon carcinogenesis induced by a single injection of 1,2-dimethylhydrazine in rats

The purpose of this study was to determine if high levels of dietary calcium could inhibit the induction of colon tumors in rats injected with a single dose of 1,2-dimethylhydrazine (DMH). Rats were given a single subcutaneous injection of DMH (200 mg/kg body weight) 2 wk before they were fed purified diets containing 5% fat and four different levels of calcium (as calcium gluconate). After 8 mo, the following incidences of colon tumors (total) were seen: 0.2% Ca, 56%; 0.5% Ca [National Academy of Sciences/National Research Council (NAS/NRC) recommended level], 75%; 1.0% Ca, 61%; 2.0% Ca, 41%. Thus, rats fed calcium at levels above or below the NAS/NRC recommendation had lower tumor incidences. The total tumor incidence and the incidence of adenocarcinomas (with or without invasion) were not significantly affected by calcium, but the incidences of benign adenomatous polyps and of distal colon tumors were significantly affected. Autoradiographic examination of [³H]thymidine-treated rats revealed that the level of calcium did not significantly alter the cell kinetic indices in the distal colon. In the proximal colon, however, the 0.2% Ca group had a significantly larger proliferative zone, with significantly more labeled cells present at the bottom of the colon crypt. Mineral analysis of tibias and serum samples revealed that rats fed higher levels of calcium had lower bone Fe and serum Mg contents, but no significant trends were seen for Ca, P, Zn or Cu. Therefore, increasing or decreasing the calcium content above or below the NAS/NRC recommendation (supplemented to low fat diets) during the promotional phase of colon carcinogenesis altered the tumor incidence, but the effect was confined to the distal colon and to benign adenomatous polyps.