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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2005-2-7
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pubmed:abstractText |
Previous studies have demonstrated that mice lacking a functional folate binding protein 2 gene (Folbp2-/-) were significantly more sensitive to in utero arsenic exposure than were the wild-type mice similarly exposed. When these mice were fed a folate-deficient diet, the embryotoxic effect of arsenate was further exacerbated. Contrary to expectations, studies on 24-h urinary speciation of sodium arsenate did not demonstrate any significant difference in arsenic biotransformation between Folbp2-/- and Folbp2+/+ mice. To better understand the influence of folate pathway genes on arsenic embryotoxicity, the present investigation utilized transgenic mice with disrupted folate binding protein 1 (Folbp1) and reduced folate carrier (RFC) genes. Because complete inactivation of Folbp1 and RFC genes results in embryonic lethality, we used heterozygous animals. Overall, no RFC genotype-related differences in embryonic susceptibility to arsenic exposure were observed. Embryonic lethality and neural tube defect (NTD) frequency in Folbp1 mice was dose-dependent and differed from the RFC mice; however, no genotype-related differences were observed. The RFC heterozygotes tended to have higher plasma levels of S-adenosylhomocysteine (SAH) than did the wild-type controls, although this effect was not robust. It is concluded that genetic modifications at the Folbp1 and RFC loci confers no particular sensitivity to arsenic toxicity compared to wild-type controls, thus disproving the working hypothesis that decreased methylating capacity of the genetically modified mice would put them at increased risk for arsenic-induced reproductive toxicity.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Arsenates,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Folate Receptors, GPI-Anchored,
http://linkedlifedata.com/resource/pubmed/chemical/Folic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Transport Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cell Surface,
http://linkedlifedata.com/resource/pubmed/chemical/Reduced Folate Carrier Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Slc19a1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/sodium arsenate
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0041-008X
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pubmed:author |
pubmed-author:FinnellRichard HRH,
pubmed-author:GouldAmyA,
pubmed-author:JamesJillJ,
pubmed-author:KappenClaudiaC,
pubmed-author:LeChrisC,
pubmed-author:LuXiufenX,
pubmed-author:MelnykStepanS,
pubmed-author:PiedrahitaJorge AJA,
pubmed-author:SalbaumJ MichaelJM,
pubmed-author:SelhubJacobJ,
pubmed-author:SpiegelsteinOferO,
pubmed-author:TroenAronA,
pubmed-author:TsieMarleneM,
pubmed-author:WlodarczykBogdanB
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
203
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
18-26
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:15694460-Animals,
pubmed-meshheading:15694460-Arsenates,
pubmed-meshheading:15694460-Biological Transport,
pubmed-meshheading:15694460-Carrier Proteins,
pubmed-meshheading:15694460-Chimera,
pubmed-meshheading:15694460-Female,
pubmed-meshheading:15694460-Folate Receptors, GPI-Anchored,
pubmed-meshheading:15694460-Folic Acid,
pubmed-meshheading:15694460-Folic Acid Deficiency,
pubmed-meshheading:15694460-Genotype,
pubmed-meshheading:15694460-Male,
pubmed-meshheading:15694460-Membrane Transport Proteins,
pubmed-meshheading:15694460-Mice,
pubmed-meshheading:15694460-Mice, Inbred C57BL,
pubmed-meshheading:15694460-Mice, Knockout,
pubmed-meshheading:15694460-No-Observed-Adverse-Effect Level,
pubmed-meshheading:15694460-Receptors, Cell Surface,
pubmed-meshheading:15694460-Reduced Folate Carrier Protein,
pubmed-meshheading:15694460-Reproduction
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pubmed:year |
2005
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pubmed:articleTitle |
Developmental consequences of in utero sodium arsenate exposure in mice with folate transport deficiencies.
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pubmed:affiliation |
Center for Environmental and Genetic Medicine, Institute of Biosciences and Technology, Texas A&M University System Health Science Center, Houston, TX 77030, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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