title: Supplemental dietary folic acid has no effect on chromosome damage in erythrocyte progenitor cells of mice.
abstract: Folate deficiency can cause chromosome damage, which could result from reduced de novo thymidylate synthesis or DNA hypomethylation. High folic acid intake has been hypothesized to inhibit folate-dependent one-carbon metabolism, which could also lead to DNA damage. A large proportion of the general population may have high folic acid intakes. In this study, 2 experiments were conducted to examine the effects of folate on chromosome damage. First, male mice were fed folic acid-deficient (D) (0 mg folic acid/kg diet), control (C) (2 mg/kg), or folic acid-supplemented (S) (6 mg folic acid/kg diet) diets from weaning to maturity. Second, female mice were fed the D, C, or S diet throughout pregnancy, lactation, and breeding for 3 generations; male mice from the F3 generation were fed the same diet as their mothers from weaning, producing D, C, and S F3 male mice. RBC micronucleus frequencies, a measure of chromosome damage or aneuploidy, were determined for both experimental groups. In mice fed diets from weaning to maturity, erythrocyte micronucleus frequency was 24% greater in D compared with C mice. F3 mice fed diet D had 260% and 174% greater reticulocyte and erythrocyte micronucleus frequencies compared with F3 C mice, respectively. The S diets did not affect micronucleus frequency, suggesting that excess folic acid at this level does not promote or protect against chromosome damage. The results suggest that chronic exposure to folic acid at the levels similar to those achieved through fortification is unlikely to be clastogenic or aneugenic.
authors.affiliation: Environmental Health Science and Research Bureau, Health Canada, Ottawa, Canada.
authors.forename: Breanne G
authors.initials: BG
authors.lastname: Swayne
authors.forename: Nathalie A
authors.initials: NA
authors.lastname: Behan
authors.forename: Andrew
authors.initials: A
authors.lastname: Williams
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Stover
authors.forename: Carole L
authors.initials: CL
authors.lastname: Yauk
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: MacFarlane
mesh_terms: D000821:Animal Feed; D000818:Animals; D025063:Chromosome Disorders / Q000139:chemically induced* / Q000178:diet therapy / Q000235:genetics; D019175:DNA Methylation / Q000187:drug effects; D019587:Dietary Supplements; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D005260:Female; D005492:Folic Acid / Q000494:pharmacology*; D005494:Folic Acid Deficiency / Q000178:diet therapy / Q000235:genetics / Q000517:prevention & control*; D005527:Food, Fortified; D042822:Genomic Instability / Q000187:drug effects* / Q000235:genetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced; D023461:Myeloid Progenitor Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000178:diet therapy / Q000235:genetics; D012156:Reticulocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D014803:Vitamin B Complex / Q000494:pharmacology; D014886:Weaning
chemical_list: D014803:Vitamin B Complex; D005492:Folic Acid