Supra-physiological folic acid concentrations induce aberrant DNA methylation in normal human cells in vitro

• Published in: Epigenetics Vol. 7; no. 7; pp. 689 - 694
• Main Authors: Charles, Michelle A, Johnson, Ian T, Belshaw, Nigel J
• Format: Journal Article
• Language: English
• Published: United States 01.07.2012
• Subjects: Binding; Biology; Bioscience; Calcium; Cancer; Cell; Cell Line; CpG Islands - drug effects; Cycle; DNA Methylation - drug effects; Enterocytes - drug effects; Enterocytes - metabolism; Fibroblasts - drug effects; Fibroblasts - metabolism; Folic Acid - pharmacology; Humans; Landes; Long Interspersed Nucleotide Elements - drug effects; Organogenesis; Proteins; S-Adenosylhomocysteine - metabolism; S-Adenosylmethionine - metabolism; Selenium - pharmacology
• ISSN: 1559-2294; 1559-2308
• DOI: 10.4161/epi.20461

The micronutrients folate and selenium may modulate DNA methylation patterns by affecting intracellular levels of the methyl donor S-adenosylmethionine (SAM) and/or the product of methylation reactions S-adenosylhomocysteine (SAH). WI-38 fibroblasts and FHC colon epithelial cells were cultured in the presence of two forms of folate or four forms of selenium at physiologically-relevant doses, and their effects on LINE-1 methylation, gene-specific CpG island (CGI) methylation and intracellular SAM:SAH were determined. At physiologically-relevant doses the forms of folate or selenium had no effect on LINE-1 or CGI methylation, nor on intracellular SAM:SAH. However the commercial cell culture media used for the selenium studies, containing supra-physiological concentrations of folic acid, induced LINE-1 hypomethylation, CGI hypermethylation and decreased intracellular SAM:SAH in both cell lines. We conclude that the exposure of normal human cells to supra-physiological folic acid concentrations present in commercial cell culture media perturbs the intracellular SAM:SAH ratio and induces aberrant DNA methylation.