Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/14/1998
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. Aberrant crypt foci are precancerous lesions that have been detected in human colon resections and in experimental animals treated with chemicals that cause cancer. We recently observed that the frequency of aberrant crypt foci 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. In the current study, we investigated whether the various forms of selenium would be protective against the binding of the chemical causing cancer to molecules (DNA) needed for normal cell division and function as a possible mechanism for its anticancer effects; the binding would result in uncontrolled division (cancer). Rats treated with selenite and selenate but not selenomethionine had a significant reduction in the amount of the chemical causing cancer bound to DNA in their colon. These results suggest that selenite and selenate can be protective against chemically induced colon cancer through the inhibition of the binding of cancer causing chemicals to DNA.
Technical Abstract: There is increasing evidence that selenium can protect against tumorigenesis or preneoplastic lesion development induced by chemical carcinogens. We recently observed that the frequency of aberrant crypt foci, a preneoplastic lesion for colon cancer, was significantly decreased in rats treated with 3,2'-dimethyl-4-aminobiphenyl (DMABP) and supplemented with selenite or selenate but not selenomethionine. The current study examined whether selenite, selenate or selenomethionine would be protective against DMABP-DNA adduct formation in the liver and colon of rats and thus further delineate the mechanism for the protective effects of the different chemical forms of selenium against aberrant crypt formation. Following injection of DMABP, two DNA adducts were identified in the liver and colon of rats. Supplementation with either 0.1 or 2.0 mg selenium/kg diet as either selenite or selenate but not selenomethionine significantly (p<0.05) decreased the amount of DMABP-DNA adducts in the colon but not the liver compared to animals fed a selenium deficient diet. Rats supplemented with selenomethionine had greater (p<0.05) tissue selenium concentrations and glutathione peroxidase activity than animals supplemented with selenite or selenate; however, they also had higher amounts of DMABP-DNA adduct. The protective effect of selenite and selenate against DMABP-DNA adduct formation apparently is not a result of alterations in cytochrome P450 activity, selenium status, glutathione peroxidase or glutathione transferase activities but may be related to differences in the metabolism of the different forms of selenium.