Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: March 5, 2011
Publication Date: August 1, 2011
Citation: Zeng, H., Yan, L., Cheng, W., Uthus, E.O. 2011. Dietary selenomethionine intake increases exon-specific DNA methylation of p53 gene in rat liver and colon mucosa. Journal of Nutrition. 141(8):1464-1468. Interpretive Summary: Colon cancer accounts for 130,000 new cancer cases and approximately 56,000 deaths each year in the United States, and it is estimated that half of Western population can expect to develop at least one colorectal tumor by age 70. Epidemiological evidence indicates that Se status is inversely associated with cancer risk, and results from intervention studies show that high Se intakes effectively reduce the risk of mammary, prostate, lung, colon, and liver cancer. However, the molecular mechanism(s) for these effects still remain poorly characterized. In this study, three groups of rats (n =6-7 /group) were fed the AIN-93G diet supplemented with 0, 0.15, or 4 mg Se (as L-selenomethionine)/kg diet for 104 days, respectively. We found that the long term Se consumption not only affects Se contained enzyme activities, homocysteine level and tissue Se contents but also produces an opposing effect on the methylation of globe genomic DNA and tumor suppressor p53 gene. The information will be useful for scientists and health-care professionals who are interested in using selenium as a nutrient and cancer prevention.
Technical 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. Our previous studies suggest that dietary selenium (Se) may alter DNA methylation, and the purpose of this study was to investigate whether long term consumption of dietary Se affects the methylation of genomic DNA, exon-specific p53 DNA gene. Three groups of rats (n =6-7 /group) were fed the AIN-93G basal diet supplemented with 0 (Se deficient), 0.15 (Se adequate), or 4 mg (Se supranutritional) (Se as L-selenomethionine)/kg diet for 104 days, respectively. Rats fed Se deficient or supranutritional diet had greater plasma and liver glutathione peroxidase activity, liver thioredoxin reductase activity and plasma homocysteine level than those without Se supplementation. However, compared with Se adequacy, Se supranutrion did not further increase these Se dependent enzyme activities and homocysteine level. In contrast, Se contents in kidney, liver, gastrocnemus muscle and plasma were increased in a Se-dose dependent manner. Interestingly, rats fed Se supranutritional diet significantly decreased global genomic DNA methylation in rat liver. However, Se supranutritional diet greatly increased the methylation of p53 gene (exons 5–8) but not B-actin gene (exon 2-3) DNA in liver and colon mucosa. Taken together, the long term Se consumption not only affects Se contained enzyme activities, homocysteine level and tissue Se contents but also produces an opposing effect on the methylation of globe genomic DNA and tumor suppressor p53 gene.