Effects of dietary folate intake and folate binding protein-2 (Folbp2) on urinary speciation of sodium arsenate in mice

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.