Document Detail


Dietary folate and selenium affect dimethylhydrazine-induced aberrant crypt formation, global DNA methylation and one-carbon metabolism in rats.
MedLine Citation:
PMID:  12949386     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Several observations suggest a role for DNA methylation in cancer pathogenesis. Although both selenium 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 selenium and folate. Weanling, Fischer-344 rats (n = 23/diet) were fed diets containing 0 or 2.0 mg selenium (as selenite)/kg and 0 or 2.0 mg folate/kg in a 2 x 2 factorial design. After 3 and 4 wk of a 12-wk experiment, 19 rats/diet were injected intraperitoneally with dimethylhydrazine (DMH, 25 mg/kg) and 4 rats/diet were administered saline. Selenium deficiency decreased (P < 0.05) colonic DNA methylation and the activities of liver DNA methyltransferase and betaine homocysteine methyltransferase and increased plasma glutathione concentrations. Folate deficiency increased (P < 0.05) the number of aberrant crypts per aberrant crypt foci, the concentration of colonic S-adenosylhomocysteine and the activity of liver cystathionine synthase. Selenium and folate interacted (P < 0.0001) to influence one-carbon metabolism and cancer susceptibility such that the number of aberrant crypts and the concentrations of plasma homocysteine and liver S-adenosylhomocysteine were the highest and the concentrations of plasma folate and liver S-adenosylmethionine and the activity of liver methionine synthase were the lowest in rats fed folate-deficient diets and supplemental selenium. These results suggest that selenium deprivation ameliorates some of the effects of folate deficiency, probably by shunting the buildup of homocysteine (as a result of folate deficiency) to glutathione.
Authors:
Cindy D Davis; Eric O Uthus
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Journal of nutrition     Volume:  133     ISSN:  0022-3166     ISO Abbreviation:  J. Nutr.     Publication Date:  2003 Sep 
Date Detail:
Created Date:  2003-09-01     Completed Date:  2003-10-28     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  0404243     Medline TA:  J Nutr     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2907-14     Citation Subset:  IM    
Affiliation:
US Department of Agriculture, Grand Forks Human Nutrition Research Center, Grand Forks, ND 58202-9034, USA. davisci@mail.nih.gov
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MeSH Terms
Descriptor/Qualifier:
5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / metabolism
Animals
Antioxidants / administration & dosage*
Carbon / metabolism*
Carcinogens / administration & dosage*
Colon / drug effects*,  metabolism,  pathology*
Cystathionine beta-Synthase / metabolism
DNA (Cytosine-5-)-Methyltransferase / metabolism
DNA Methylation
Deficiency Diseases / genetics,  metabolism,  pathology
Diet
Dimethylhydrazines / administration & dosage*
Disease Susceptibility
Drug Interactions
Folic Acid / administration & dosage*,  blood
Glutathione / blood
Homocysteine / blood
Injections, Intraperitoneal
Liver / enzymology,  metabolism
Male
Rats
Rats, Inbred F344
S-Adenosylhomocysteine / metabolism
Selenium / administration & dosage*,  deficiency
Chemical
Reg. No./Substance:
0/Antioxidants; 0/Carcinogens; 0/Dimethylhydrazines; 454-28-4/Homocysteine; 59-30-3/Folic Acid; 70-18-8/Glutathione; 7440-44-0/Carbon; 7782-49-2/Selenium; 979-92-0/S-Adenosylhomocysteine; EC 2.1.1.13/5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; EC 2.1.1.37/DNA (Cytosine-5-)-Methyltransferase; EC 4.2.1.22/Cystathionine beta-Synthase

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