Effects of the experimental chemopreventative agent, glucarate, on intestinal carcinogenesis in rats.

ABSTRACT

Dietary calcium glucarate was previously shown to protect effectively against chemically-induced mammary, lung, liver and skin carcinogenesis in rodents, whereas the negative dietary calcium control, calcium gluconate, had no effect. In the present study the chemopreventative activity of dietary calcium glucarate was evaluated in the azoxymethane intestinal carcinogenesis model using the Fischer strain rat. The protocol limited the duration of azoxymethane treatment to 3 weeks to permit the evaluation of the separate effects of glucarate on the initiation and promotion phases. Control rats, treated with azoxymethane and maintained on a low fat chow diet throughout the 32-week experiment had an intestinal adenocarcinoma incidence of 55%, with an equal incidence of 27.7% in the small and large intestines. There was no significant difference between this control group and a negative calcium control group fed 128 mmol/kg chow of calcium as calcium gluconate. In contrast to these two control groups, supplementation of the diet of azoxymethane-treated rats with 128 mmol/kg diet of calcium glucarate during both the initiation and promotion phases significantly inhibited the overall induction of adenocarcinomas in the intestine, the incidence in the entire intestine and in the small and large intestines being 11.8, 5.8 and 5.8%, respectively. When fed only during the initiation phase, the inhibition again was statistically significant, the corresponding values being 11.8%, 5.8 and 5.8%. When calcium glucarate was fed during the promotion phase, a statistically significant inhibition of adenocarcinoma induction was observed only in the colon where the incidence was 5.5%. Weight gain was similar in all groups. These and related data indicate that dietary glucarate exerts a significant inhibitory effect on azoxymethane-induced intestinal and in particular colon carcinogenesis in the rat, decreasing their incidence and size and reducing their metastic potential.