Dietary selenium and arsenic affect DNA methylation in vitro in Caco-2 cells and in vivo in rat liver and colon

Selenium is an essential trace element for human health, and it has receive d considerable attention for its possible role as an anticarcinogenic agent . The purpose of the present study was to determine whether changes in the amount and the chemical form of selenium would affect DNA methylation and w hether this effect would be modified by arsenic. Caco-2 cells, a human colo n cancer cell line, were exposed to 0, 1 or 2 mu mol supplemental selenite/ L and 0, 1 or 2 mu mol supplemental arsenite/L for 7 d. DNA isolated from C aco-2 cells not treated with selenite was significantly (P < 0.0001) hypome thylated compared with that from cells treated with 1 or 2 <mu>mol selenite /L. DNA isolated from Caco-2 cells not treated with arsenite was significan tly (P < 0.0001) hypomethylated compared with DNA isolated from cells treat ed with 1 or 2 <mu>mol arsenite/L. In addition, methylation of the p53 prom oter region of Caco-2 cells decreased when cells were cultured in the absen ce of selenite and in the absence of arsenite. Sixty weanling male Fischer 344 rats were fed a torula yeast-based diet supplemented with 0, 0.1 or 2 m g selenium/kg diet as either selenite or selenomethionine in the presence o r absence of 5 mg arsenic/kg diet as arsenite for 6 wk. Similar to the resu lts with Caco-2 cells, rats fed selenium-deficient diets had significantly (P < 0.0001) hypomethylated liver and colon DNA compared with rats fed 0.1 or 2.0 <mu>g selenium/g diets as either selenite or selenomethionine. Thus, alterations in DNA methylation may be a potential mechanism, whereby defic ient dietary selenium increases liver and colon tumorigenesis.