| First Author | Spiegelstein O | Year | 2005 |
| Journal | Toxicol Appl Pharmacol | Volume | 203 |
| Issue | 1 | Pages | 18-26 |
| PubMed ID | 15694460 | Mgi Jnum | J:95928 |
| Mgi Id | MGI:3528107 | Doi | 10.1016/j.taap.2004.07.006 |
| Citation | Spiegelstein O, et al. (2005) Developmental consequences of in utero sodium arsenate exposure in mice with folate transport deficiencies. Toxicol Appl Pharmacol 203(1):18-26 |
| 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. |
