Inhibition of progression of aberrant crypt foci and colon tumor development by vitamin E and beta-carotene in rats on a high-risk diet.

Abstract

In this study we evaluated the effect of dietary administration of a high-fat, low-fiber diet (HRD) supplemented with Vitamin E, beta-carotene or folic acid and wheat bran on the growth of pre-existing aberrant crypt foci (ACF) that had been induced in Fischer-344 rats exposed to azoxymethane (AOM) and a HRD for 10 weeks. The rats (25 rats/dietary group) were fed a HRD for 2 weeks and were then given 2 subcutaneous injections of AOM (15 mg/kg body weight) while the rats continued on the HRD. After 6 weeks, rats were either maintained on the HRD (control) or crossed over to a HRD containing non-toxic levels of either Vitamin E, beta-carotene, folic acid or wheat bran. At 10, 14 and 18 weeks after the initiation of the experiment, 5 rats from each group were killed and the number of aberrant crypt foci (ACF) with different multiplicities were compared between groups. The dietary intervention was continued for 30 weeks to determine whether the inhibitory effect on the growth of ACF influenced the subsequent development of colonic tumors. The results revealed that vitamin E and beta-carotene caused a significant decrease in the number of ACF of different multiplicities when compared to the effect of the HRD alone. The decrease in the number of ACF due to folic acid and wheat bran appeared to be much smaller and in most cases was not significant. However, there was also a significant decrease in the incidence of colonic tumors and tumor multiplicity in both the vitamin E and beta-carotene groups that was not seen in the control group. The reports clearly demonstrates the ability of vitamin E and beta-carotene to inhibit the growth of colonic ACF, even in the presence of the strong promoting effect of high levels of dietary fat, using a post-initiation experimental design.