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.
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.
- Folate deficiency
- Folic acid