Dietary selenium reduces the formation of aberrant crypts in rats administered 3,2 '-dimethyl-4-aminobiphenyl

Human epidemiologic studies suggest that low seleniun status is associated with increased cancer risk and that selenium supplementation is associated with reduction in the incidence of several cancers, including colorectal ca ncer. Aroma and heterocyclic amine carcinogens are thought to be important in the etiology of human colorectal cancer, but no information is available on the effects of selenium on aromatic amine-induced colon cancer. In orde r to investigate this effect, aberrant crypt foci (ACF), the putative prene oplastic lesions of colon cancer in humans and rodents, were used as a biom arker to test the hypothesis that selenium supplementation can reduce aroma tic amine-induced colon carcinogenesis. Male weanling F344 inbred rats were fed a basal torula yeast selenium-deficient diet supplemented with 0, 0.1, or 2.0 mg selenium/kg diet as selenite, selenate, or selenomethionine (SeM et). Animals were fed the diets for 4 weeks and then administered 1 sc inje ction/week for 2 weeks of 3,2'-dimethyl-4-aminobiphenyl (DMABP; 100 mg/kg) or vehicle peanut oh). At 12 weeks, the rats were euthanized and the colon and rectum were removed, opened longitudinally, and fixed in 70% ethanol. G lutathione peroxidase activities in erythrocytes and liver cytosol and sele nium concentrations in the colon/rectum and kidney increased significantly (p < 0.05) and in a dose-dependent manner with each of the three selenium d iets. No ACF were identified in vehicle-treated rats; In DMABP-treated rats , ACF frequencies decreased significantly (p < 0.05) in groups supplemented with 0.1 or 2.0 mg selenium/kg diet as selenite and selenate but not SeMet . There were no significant differences in ACF and aberrant crypts between rats fed 0.1 vs 2.0 mg selenium/kg diet. These results suggest that dietary selenium, depending on chemical form, can reduce aromatic amine-induced co lon carcinogenesis. (C) 1999 Academic Press.