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Global DNA and p53 region-specific hypomethylation in human colonic cells is induced by folate depletion and reversed by folate supplementation.

Wasson, Gillian R., McGlynn, Angela P., McNulty, Helene, O`Reilly, Sharleen, McKelvey-Martin, Valerie, McKerr, George, Strain, J. J., Scott, John and Downes, Stephen C. 2006, Global DNA and p53 region-specific hypomethylation in human colonic cells is induced by folate depletion and reversed by folate supplementation., Journal of nutrition, vol. 136, no. 11, pp. 2748-2753.

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Title Global DNA and p53 region-specific hypomethylation in human colonic cells is induced by folate depletion and reversed by folate supplementation.
Author(s) Wasson, Gillian R.
McGlynn, Angela P.
McNulty, Helene
O`Reilly, SharleenORCID iD for O`Reilly, Sharleen orcid.org/0000-0003-3547-6634
McKelvey-Martin, Valerie
McKerr, George
Strain, J. J.
Scott, John
Downes, Stephen C.
Journal name Journal of nutrition
Volume number 136
Issue number 11
Start page 2748
End page 2753
Publisher American Society for Nutrition
Place of publication Bethesda, Md.
Publication date 2006-11
ISSN 0022-3166
1541-6100
Summary There is increasing evidence to suggest that reduced folate status may be a causative factor in carcinogenesis, particularly colorectal carcinogenesis. Folate is essential for the synthesis of S-adenosylmethionine, the methyl donor required for all methylation reactions in the cell, including the methylation of DNA. Global DNA hypomethylation appears to be an early, and consistent, molecular event in carcinogenesis. We have examined the effects of folate depletion on human-derived cultured colon carcinoma cells using 2 novel modifications to the Comet (single cell gel electrophoresis) assay to detect global DNA hypomethylation and gene region–specific DNA hypomethylation. Colon cells cultured in folate-free medium for 14 d showed a significant increase in global DNA hypomethylation compared with cells grown in medium containing 3µmol/L folic acid. This was also true at a gene level, with folate-deprived cells showing significantly more DNA hypomethylation in the region of the p53 gene. In both cases, the effects of folate depletion were completely reversed by the reintroduction of folic acid to the cells. These results confirm that decreased folate levels are capable of inducing DNA hypomethylation in colon cells and particularly in the region of the p53 gene, suggesting that a more optimal folate status in vivo may normalize any DNA hypomethylation, offering potential protective effects against carcinogenesis. This study also introduces 2 novel functional biomarkers of DNA hypomethylation and demonstrates their suitability to detect folate depletion–induced molecular changes.
Language eng
Field of Research 111299 Oncology and Carcinogenesis not elsewhere classified
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2006, American Society for Nutrition
Persistent URL http://hdl.handle.net/10536/DRO/DU:30006541

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