title: Arsenic urinary speciation in Mthfr deficient mice injected with sodium arsenate.
abstract: In most mammalian species, arsenic biotransformation occurs primarily by biomethylation and reduction reactions, with dimethylarsinic acid being the predominant metabolite excreted in the urine. Methylenetetrahydrofolate reductase (Mthfr) plays a key role in folate metabolism by channeling one-carbon units between nucleotide synthesis and methylation reactions. In the study on transgenic Mtfhr knockout mice we investigated: (1) whether Mthfr is an important determinant in arsenic biotransformation by performing urinary arsenic speciation, and (2) whether dietary folate deficiency alters arsenic biotransformation in these mice. The Mthfr mice fed folate replete or folate deficient diet were injected with sodium arsenate 1mg/kg, and placed in metabolic cages for a urine collection. The urine was analyzed for arsenic species. Additionally, folate and homocysteine plasma level was analyzed in Mthfr mice. When fed a folate control diet, the Mthfr(-/-) mice excreted significantly less of the total arsenic in urine than did the Mthfr(+/+) and Mthfr(+/-) mice. The Mthfr(-/-) had significantly lower levels of pentavalent arsenic in their urine than did the Mthfr(+/+)mice. The wild type mice excreted significantly less pentavalent arsenic when they were fed folate deficient diet comparing to control diet. The current data suggest that both the Mthfr status and food folate level modulate in a significant manner excretion of arsenic in mice, following intraperitoneal administration of sodium arsenate.
authors.affiliation: Center for Environmental and Genetic Medicine, Institute of Biosciences and Technology, Texas A&M University System Health Science Center, Houston, TX 77030, USA. bwlodarczyk@austin.utexas.edu
authors.forename: Bogdan
authors.initials: B
authors.lastname: Wlodarczyk
authors.forename: Ofer
authors.initials: O
authors.lastname: Spiegelstein
authors.forename: Denise
authors.initials: D
authors.lastname: Hill
authors.forename: X Chris
authors.initials: XC
authors.lastname: Le
authors.forename: Richard H
authors.initials: RH
authors.lastname: Finnell
mesh_terms: D000818:Animals; D001149:Arsenates / Q000378:metabolism* / Q000633:toxicity / Q000652:urine*; D018592:Cross-Over Studies; D004032:Diet / Q000662:veterinary; D005260:Female; D005492:Folic Acid / Q000494:pharmacology; D005494:Folic Acid Deficiency; D005838:Genotype; D006710:Homocysteine / Q000097:blood; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D011897:Random Allocation; D013432:Sulfathiazoles / Q000494:pharmacology
chemical_list: D001149:Arsenates; D013432:Sulfathiazoles; D006710:Homocysteine; C009277:sodium arsenate; D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2); C009342:succinylsulfathiazole