title: Dietary selenomethionine increases exon-specific DNA methylation of the p53 gene in rat liver and colon mucosa.
abstract: The regulation of site-specific DNA methylation of tumor suppressor genes has been considered as a leading mechanism by which certain nutrients exert their anticancer property. This study was to investigate whether selenium (Se) affects the methylation of globe genomic DNA and the exon-specific p53 gene. Three groups of rats (n = 6-7/group) were fed the AIN-93G basal diet supplemented with 0 [Se deficient (D)], 0.15 [Se adequate (A)], or 4 mg [Se supranutritional (S)] (Se as l-selenomethionine)/kg diet for 104 d, respectively. Rats fed the A or S diet had greater plasma and liver glutathione peroxidase activity, liver thioredoxin reductase activity, and plasma homocysteine concentration than those fed the D diet. However, compared with the A diet, rats fed the S diet did not further increase these Se-dependent enzyme activities or homocysteine concentration. In contrast, Se concentrations in kidney, liver, gastrocnemius muscle, and plasma were increased in a Se-dose-dependent manner. Interestingly, rats fed the S diet had significantly less global liver genomic DNA methylation than those fed the D diet. However, the S diet significantly increased the methylation of the p53 gene (exons 5-8) but not the β-actin gene (exons 2-3) DNA in liver and colon mucosa compared with those fed the D diet. Taken together, long-term Se consumption not only affects selenoprotein enzyme activities, homocysteine, tissue Se concentrations, and global genomic DNA methylation but also increases exon-specific DNA methylation of the p53 gene in a Se-dose-dependent manner in rat liver and colon mucosa.
authors.affiliation: USDA, Agricultural Research Service, Grand Forks Human Nutrition Research Center, Grand Forks, ND 58203, USA. huawei.zeng@ars.usda.gov
authors.forename: Huawei
authors.initials: H
authors.lastname: Zeng
authors.forename: Lin
authors.initials: L
authors.lastname: Yan
authors.forename: Wen-Hsing
authors.initials: WH
authors.lastname: Cheng
authors.forename: Eric O
authors.initials: EO
authors.lastname: Uthus
mesh_terms: D000818:Animals; D003106:Colon / Q000378:metabolism*; D019175:DNA Methylation; D005091:Exons; D016158:Genes, p53; D005979:Glutathione Peroxidase / Q000097:blood; D006710:Homocysteine / Q000097:blood; D007413:Intestinal Mucosa / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D016133:Polymerase Chain Reaction; D051381:Rats; D017207:Rats, Sprague-Dawley; D012645:Selenomethionine / Q000008:administration & dosage*
chemical_list: D006710:Homocysteine; D012645:Selenomethionine; D005979:Glutathione Peroxidase