Effects of dietary folate intake and folate binding protein-1 (Folbp1) on urinary speciation of sodium arsenate in mice.
In most mammalian species, arsenic biotransformation occurs primarily by biomethylation with dimethylarsinic acid being the predominant metabolite excreted in the urine. Folbp1 (folate binding protein-1) mediated intracellular folate uptake is one route by which cells harvest folate cofactors. In light of the likely relationship between folate biochemistry and arsenic biotransformation, our experiments were designed to test: (1) whether Folbp1 is an important determinant in arsenic biotransformation, by performing urinary arsenic speciation in Folbp1 nullizygous (Folbp1(-/-)) and wildtype control mice, and (2) whether dietary folate deficiency alters arsenic biotransformation in these mice. Compared to normal folate intake, folate deficiency caused lower amounts of arsenic to be excreted in the urine of both the wildtype controls and Folbp1(-/-) mice. Folbp1(-/-) mice excreted more dimethylarsinic acid than wildtype control mice during folate deficiency, but not during normal folate intake. The present data suggest that inadequate folate intake may result in decreased biotransformation and excretion of arsenic, which is likely to increase arsenic exposure and related toxicities.
Center for Environmental and Genetic Medicine, Institute of Biosciences and Technology, Texas A&M University System Health Science Center, 77030, Houston, TX, USA. ospiegelstein@ibt.tamu.edu
Ofer
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Spiegelstein
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X Chris
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Aron
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Troen
Jacob
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Selhub
Stepan
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Melnyk
S Jill
SJ
James
Richard H
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Finnell
D000818:Animals; D001149:Arsenates / Q000652:urine*; D001151:Arsenic / Q000378:metabolism / Q000633:toxicity / Q000652:urine; D020261:Arsenic Poisoning / Q000652:urine*; D001152:Arsenicals / Q000652:urine; D018053:Arsenites / Q000652:urine; D002101:Cacodylic Acid / Q000652:urine; D002352:Carrier Proteins / Q000378:metabolism*; D018592:Cross-Over Studies; D058973:Folate Receptors, GPI-Anchored; D005492:Folic Acid / Q000097:blood / Q000378:metabolism*; D005494:Folic Acid Deficiency / Q000378:metabolism / Q000652:urine*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011956:Receptors, Cell Surface; D012435:S-Adenosylhomocysteine / Q000097:blood; D012436:S-Adenosylmethionine / Q000097:blood
D001149:Arsenates; D001152:Arsenicals; D018053:Arsenites; D002352:Carrier Proteins; D058973:Folate Receptors, GPI-Anchored; D011956:Receptors, Cell Surface; D012436:S-Adenosylmethionine; D005492:Folic Acid; D012435:S-Adenosylhomocysteine; D002101:Cacodylic Acid; C020300:monomethylarsonic acid; C015001:arsenite; D001151:Arsenic; C025657:arsenic acid