Arsenic-induced congenital malformations in genetically susceptible folate binding protein-2 knockout mice
| Autor: | Richard H. Finnell, Xiufen Lu, Janee Gelineau-van Waes, Ofer Spiegelstein, Christopher Le, Bogdan J. Wlodarczyk, Roseann L. Vorce |
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| Rok vydání: | 2001 |
| Předmět: |
Genotype
Arsenites chemistry.chemical_element Receptors Cell Surface Exencephaly Biology Folic Acid Deficiency Toxicology Arsenicals Andrology chemistry.chemical_compound Mice Pregnancy medicine Animals Cacodylic Acid Genetic Predisposition to Disease Neural Tube Defects Homocysteine Arsenic Pharmacology Mice Knockout Dose-Response Relationship Drug Folate Receptors GPI-Anchored Fetal Resorption medicine.disease Folate-binding protein Teratology Dose–response relationship Teratogens chemistry In utero Prenatal Exposure Delayed Effects Immunology Knockout mouse Arsenates Female Sodium arsenate Carrier Proteins |
| Zdroj: | Toxicology and applied pharmacology. 177(3) |
| ISSN: | 0041-008X |
| Popis: | Arsenic is a well-known carcinogen, which has been suspected of being a human teratogen, although there is currently insufficient and inadequate supportive data to make any definitive judgments. In addition, the significance of individual genetic differences on pregnancy outcomes following in utero exposure to arsenic is currently unknown. In order to better understand the role of folate transport mechanisms in arsenic-induced neural tube defects, we examined the effect of in utero exposure to sodium arsenate in a genetically altered murine model in which the folate binding protein 2 (Folbp2) gene has been inactivated by homologous recombination. In utero sodium arsenate exposure induced exencephaly in 40.6% of Folbp2(-/-) embryos compared with 24.0% in control Folbp2(+/+) embryos. The differences in response frequencies were further exacerbated when the dams were fed a folate-deficient diet. Under these conditions, exencephaly was observed in 64.0% of Folbp2(-/-) embryos compared with 25.7% in control Folbp2(+/+) embryos. Analysis of arsenic metabolites excreted in the urine following sodium arsenate injection to Folbp2(-/-) and Folbp2(+/+) mice indicated that there were no significant differences in arsenic metabolism between the two groups. Thus, the increased susceptibility of Folbp2(-/-) mice to arsenate-induced teratogenicity may not be due to differences in biomethylation and exposure. In conclusion, the data suggest that impaired folate transport in the developing mouse embryo increases the risk for developmental defects following in utero exposure to sodium arsenate and that these differences are not due to differences in metabolism of arsenic. |
| Databáze: | OpenAIRE |
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