Folate binding protein-2 (Folbp2 -/-) knockout mice have been previously shown to be highly susceptible to the teratogenic effects of arsenic. Arsenic biotransformation is achieved primarily by biomethylation. Given the potential close relationship between folate biochemistry and arsenic biotransformation, the aims of our study were to: (1) test whether Folbp2 -/- mice have altered arsenic biotransformation which would suggest a potential mechanism for their enhanced susceptibility; (2) examine whether dietary folate deficiency alters arsenic biotransformation. Folbp2 -/- mice were found to have slightly lower plasma folate levels than wildtype mice. No genotype-specific effects were observed in arsenic speciation thereby negating altered biotransformation of arsenic as the mechanism of the enhanced teratogenicity seen in Folbp2 -/- mice. Reduction in excretion of organic arsenicals was observed during folate deficiency, suggesting an important role for folic acid homeostasis in arsenic biotransformation.
Bibliographical noteFunding Information:
This project was supported in part by grants ES 04917, ES 09106 and ES 11775 from the National Institute of Environmental Health to RHF; grants from the Natural Sciences and Engineering Research Council of Canada and Canadian Water Networks NCE to XCL. The paper's contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIEHS, NIH. The authors would like to thank Ms. Michelle Merriweather, Ms. Marlene Tsie, and Mr. Joe Wicker from the Center for Environmental and Genetic Medicine at the Institute of Biosciences and Technology, Texas A&M University System HSC for their assistance in this study; Ms. Marie Nadeau from the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University for assisting with the folate determination assays; Dr. Laura E. Mitchell from the Department of Environmental and Genetic Medicine at the Institute of Biosciences and Technology, Texas A&M University System HSC for assisting with the statistical analysis.
- Folic acid
- Urinary speciation