title: Supra-physiological folic acid concentrations induce aberrant DNA methylation in normal human cells in vitro.
abstract: 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.
authors.affiliation: Institute of Food Research, Norwich Research Park, Norwich, UK.
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Charles
authors.forename: Ian T
authors.initials: IT
authors.lastname: Johnson
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Belshaw
mesh_terms: D002460:Cell Line; D018899:CpG Islands / Q000187:drug effects; D019175:DNA Methylation / Q000187:drug effects*; D020895:Enterocytes / Q000187:drug effects / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005492:Folic Acid / Q000494:pharmacology*; D006801:Humans; D020084:Long Interspersed Nucleotide Elements / Q000187:drug effects; D012435:S-Adenosylhomocysteine / Q000378:metabolism; D012436:S-Adenosylmethionine / Q000378:metabolism; D012643:Selenium / Q000494:pharmacology
chemical_list: D012436:S-Adenosylmethionine; D005492:Folic Acid; D012435:S-Adenosylhomocysteine; D012643:Selenium