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United States Department of Agriculture

Agricultural Research Service

Title: Dietary Seleniuim (Se) and Folate Affect Dimethylhydrazine (Dmh)-Induced Aberrant Crypt Formation, Global DNA Methylation and One-Carbon Metabolism in Rats

Authors
item Davis, Cindy
item Uthus, Eric

Submitted to: Journal of Federation of American Societies for Experimental Biology
Publication Type: Abstract Only
Publication Acceptance Date: December 2, 2002
Publication Date: March 14, 2003
Citation: Davis, C.D., Uthus, E.O. 2003. Dietary selenium (SE) and folate affect dimethylhydrazine (DMH)-induced aberrant crypt formation, global DNA methylation and one-carbon metabolism in rats [abstract]. The Federation of American Societies for Experimental Biology Journal. 17:A1371.

Technical Abstract: Several observations implicate a role for DNA methylation in cancer pathogenesis. Although both Se and folate deficiency have been shown to cause global DNA hypomethylation and increased cancer susceptibility, the nutrients have different effects on one-carbon metabolism. Thus, the purpose of this study was to investigate the interactive effects of dietary Se and folate. Weanling, Fischer-344 rats (n=23/diet) were fed diets containing 0 or 2.0 ug Se (as selenite)/g and 0 or 2.0 ug folate/g in a 2 x 2 factorial design. After 3 and 4 wk of diets, 19 rats/diet were injected with DMH (25 mg/kg i.p.) and 4 rats/diet were administered saline. Se deficiency decreased liver DNA methyltransferase and betaine homocysteine methyltransferase activities and colonic DNA methylation. Se and folate had significant (p<0.0001) interactive effects on one-carbon metabolism and cancer susceptibility such that aberrant crypts, plasma homocysteine, and liver S-adenosyl-homocysteine were the highest and plasma folate, plasma B12, liver S-adenosyl-methionine and liver methionine synthase were the lowest when rats were fed deficient folate and supplemental Se. These results suggest that Se deprivation seems protective in folate deficiency, probably by shunting the buildup of homocysteine (as a result of folate deficiency) to glutathione.

Last Modified: 12/21/2014
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