Dietary selenomethionine increases exon-specific DNA methylation of the p53 gene in rat liver and colon mucosa

J Nutr. 2011 Aug;141(8):1464-8. doi: 10.3945/jn.111.140715. Epub 2011 Jun 8.

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Colon / metabolism*
  • DNA Methylation*
  • Exons*
  • Genes, p53*
  • Glutathione Peroxidase / blood
  • Homocysteine / blood
  • Intestinal Mucosa / metabolism
  • Liver / metabolism*
  • Male
  • Polymerase Chain Reaction
  • Rats
  • Rats, Sprague-Dawley
  • Selenomethionine / administration & dosage*

Substances

  • Homocysteine
  • Selenomethionine
  • Glutathione Peroxidase