INHIBITION OF PROGRESSION OF ABERRANT CRYPT FOCI AND COLON-TUMOR DEVELOPMENT BY VITAMIN-E AND BETA-CAROTENE IN RATS ON A HIGH-RISK DIET

In this study we evaluated the effect of dietary administration of a h igh-fat, low-fiber diet (HRD) supplemented with Vitamin E, beta-carote ne 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 i njections of AOM (15 mg/kg body weight) while the rats continued on th e HRD. After 6 weeks, rats were either maintained on the HRD (control) or crossed over to a HRD containing non-toxic levels of either Vitami n E, beta-carotene, folic acid or wheat bran. At 10, 14 and 18 weeks a fter the initiation of the experiment, 5 rats from each group were kil led and the number of aberrant crypt foci (ACF) with different multipl icities were compared between groups. The dietary intervention was con tinued 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 signif icant decrease in the number of ACF of different multiplicities when c ompared 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 i n most cases was not significant. However, there was also a significan t decrease in the incidence of colonic tumors and tumor multiplicity i n both the vitamin E and beta-carotene groups that was not seen in the control group, The reports clearly demonstrates the ability of vitami n E and beta-carotene to inhibit the growth of colonic ACF, even in th e presence of the strong promoting effect of high levels of dietary fa t, using a post-initiation experimental design.