Colon Carcinogenesis is Inhibited More Effectively by Phytate than by Selenium in F344 Rats Given 30 mg/kg Azoxymethane
Diets supplemented with either 2.5 ppm selenium (Se) or 2% phytate (P) in the drinking water have been reported to inhibit colon carcinogenesis in F344 rats treated with azoxymethane. Aberrant crypt foci (ACF) are putative preneoplastic lesions that can be quantified readily in unembedded segments of colon a short time after treatment with carcinogen. We wanted to test the validity of the ACF assay to assess chemopreventive agents that are given after carcinogen. Male F344 rats (age 6 weeks) were injected sc with 30 mg/kg azoxymethane (AOM) and one week later put on one of three diets until sacrifice: AIN-76A formulation of semipurified rodent chow and plain drinking water (AOM alone), AIN-76A diet supplemented with 2.5 ppm selenium and plain drinking water (AOM+Se), or AIN-76A diet and drinking water with 2% sodium phytate (AOM+P). Control rats on the three diets were injected with saline. Rats were killed at 4, 12, and 36 weeks after injection. No tumors were seen in any control group; two ACF were seen in 36-week control rats on Se; no ACF were seen in any other control rats. The tumor incidence in the AOM alone and the AOM+SE groups was 83% (10 of 12 rats) in both cases compared to 25% (3 of 12 rats) in the AOM+P group. The percentage and number of large ACF (those with 4 or more crypts) were greater (p = 0.0008 and p = 0.014, respectively, Mann-Whitney) in rats with tumors than in those without tumors at 36 weeks after injection. At 12 weeks after injection, the number of large ACF in the AOM alone or the AOM+SE group was greater (p = 0.005, Mann-Whitney test) than in the AOM+P group. Our data suggest that the number of large ACF is predictive of tumor incidence.