Submitted to: Journal of Toxicology and Applied Pharmacology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/4/1999
Publication Date: N/A
Interpretive Summary: Selenium is an essential trace element for human health and has received considerable attention for its possible role as an effective, naturally occurring, substance that has cancer preventive properties. Colon cancer is the second leading cause of cancer deaths in the United States and fourth most common cause of cancer deaths worldwide. Anatomical lesions leading to cancer have been detected in human colon resections and in experimental animals treated with chemicals that cause cancer. We observed that the frequency of these anatomical changes was significantly reduced in animals treated with a chemical causing cancer and supplemented with various selenium salts, selenate and selenite, but not when supplemented with selenomethionine, an amino acid containing selenium. These results suggest that selenite and selenate can be protective against chemically induced colon cancer.
Technical Abstract: Human epidemiologic studies suggest that low selenium status is associated with increased risks of cancer and selenium supplementation is associated with reductions in the incidence of several cancers, including colorectal cancer. Aromatic 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 order to investigate this effect, aberrant crypt foci (ACF), the putative preneoplastic lesions of colon cancer in humans and rodents, were used as a biomarker to test the hypothesis that selenium supplementation has a protective effect in aromatic 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 (SeMet). Animals were fed the diets for 4 weeks and then administered 2 weekly sc injections of 3,2'-dimethyl-4-aminobiphenyl (DMABP; 100 mg/kg) or vehicle (peanut oil). At 12 weeks, the rats were sacrificed and the colon and rectum were removed, opened longitudinally and fixed in 70% ethanol. Glutathione peroxidase activities in erythrocytes and liver cytosol, and selenium concentrations in the colon/rectum, and kidney increased significantly (p<0.05) in a dose-dependent manner with each of the three selenium diets. No ACF were identified in vehicle-treated rats. In DMABP-treated rats, ACF frequencies decreased significantly (p<0.05) in group supplemented with selenite and selenate but not SeMet. These results suggest that dietary selenium, can inhibit aromatic amine-induced colon carcinogenesis.