title: Dietary folic acid protects against genotoxicity in the red blood cells of mice.
abstract: Folate is an essential B vitamin required for the de novo synthesis of purines, thymidylate and methionine. Folate deficiency can lead to mutations and genome instability, and has been shown to exacerbate the genotoxic potential of environmental toxins. We hypothesized that a folic acid (FA) deficient diet would induce genotoxicity in mice as measured by the Pig-a mutant phenotype (CD24-) and micronuclei (MN) in reticulocytes (RET) and red blood cells/normochromatic erythrocytes (RBC/NCE). Male Balb/c mice were fed a FA deficient (0 mg/kg), control (2 mg/kg) or supplemented (6 mg/kg) diet from weaning for 18 wk. Mice fed the deficient diet had 70% lower liver folate (p < 0.001), 1.8 fold higher MN-RET (p < 0.001), and 1.5 fold higher MN-NCE (p < 0.001) than mice fed the control diet. RET(CD24-) and RBC(CD24-) frequencies were not different between mice fed the deficient and control diets. Compared to mice fed the FA supplemented diet, mice fed the deficient diet had 73% lower liver folate (p < 0.001), a 2.0 fold increase in MN-RET (p < 0.001), a 1.6 fold increase in MN-NCE (p < 0.001) and 3.8 fold increase in RBC(CD24-) frequency (p = 0.011). RET(CD24-) frequency did not differ between mice fed the deficient and supplemented diets. Our data suggest that FA adequacy protects against mutagenesis at the Pig-a locus and MN induction in the red blood cells of mice.
authors.affiliation: Nutrition Research Division, Health Canada, Ottawa, Canada. Electronic address: amanda.macfarlane@hc-sc.gc.ca.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: MacFarlane
authors.affiliation: Nutrition Research Division, Health Canada, Ottawa, Canada.
authors.forename: Nathalie A
authors.initials: NA
authors.lastname: Behan
authors.affiliation: Division of Nutritional Sciences, Cornell University, Ithaca, USA.
authors.forename: Martha S
authors.initials: MS
authors.lastname: Field
authors.affiliation: Environmental Health Science and Research Bureau, Health Canada, Ottawa, Canada.
authors.forename: Andrew
authors.initials: A
authors.lastname: Williams
authors.affiliation: Division of Nutritional Sciences, Cornell University, Ithaca, USA.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Stover
authors.affiliation: Environmental Health Science and Research Bureau, Health Canada, Ottawa, Canada.
authors.forename: Carole L
authors.initials: CL
authors.lastname: Yauk
mesh_terms: D000818:Animals; D004249:DNA Damage / Q000187:drug effects; D019587:Dietary Supplements; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005492:Folic Acid / Q000008:administration & dosage* / Q000378:metabolism; D005494:Folic Acid Deficiency / Q000178:diet therapy* / Q000235:genetics / Q000378:metabolism; D008715:Methionine / Q000378:metabolism; D051379:Mice; D012156:Reticulocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: D005492:Folic Acid; D008715:Methionine
keywords: Folic acid; Genome stability; Genotoxicity; Micronucleus; Mutation; Pig-a gene