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 received 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 whether this effect would be modified by arsenic. Caco-2 cells, a human colon cancer cell line, were exposed to 0, 1 or 2 micromol supplemental selenite/L and 0, 1 or 2 micromol supplemental arsenite/L for 7 d. DNA isolated from Caco-2 cells not treated with selenite was significantly (P: < 0. 0001) hypomethylated compared with that from cells treated with 1 or 2 micromol selenite/L. DNA isolated from Caco-2 cells not treated with arsenite was significantly (P: < 0.0001) hypomethylated compared with DNA isolated from cells treated with 1 or 2 micromol arsenite/L. In addition, methylation of the p53 promoter region of Caco-2 cells decreased when cells were cultured in the absence 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 mg selenium/kg diet as either selenite or selenomethionine in the presence or absence of 5 mg arsenic/kg diet as arsenite for 6 wk. Similar to the results 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 microg selenium/g diets as either selenite or selenomethionine. Thus, alterations in DNA methylation may be a potential mechanism, whereby deficient dietary selenium increases liver and colon tumorigenesis.
Davis
C D
CD
U.S. Department of Agriculture, Grand Forks Human Nutrition Research Center, Grand Forks, North Dakota 58202-9034, USA. cdavis@gfhnrc.ars.usda.gov
Uthus
E O
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Finley
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JW
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001151:Arsenic / Q000494:pharmacology*; D018053:Arsenites / Q000494:pharmacology; D018938:Caco-2 Cells / Q000187:drug effects* / Q000378:metabolism; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D019175:DNA Methylation / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D012643:Selenium / Q000737:chemistry / Q000494:pharmacology*; D012645:Selenomethionine / Q000494:pharmacology; D018038:Sodium Selenite / Q000494:pharmacology
D016588:Anticarcinogenic Agents; D018053:Arsenites; D012645:Selenomethionine; D012643:Selenium; D018038:Sodium Selenite; C015001:arsenite; D001151:Arsenic