| Valproic acid (VPA), a commonly used antiepileptic agent, is associated with a 1--2% incidence of neural tube defects (NTDs) when taken during pregnancy. However, the molecular mechanism of VPA-induced NTDs has not been elucidated. Previous research suggests that VPA exposure may lead to an increase in reactive oxygen species (ROS). DNA damage due to ROS can result in DNA double strand breaks (DSBs) which can be repaired through homologous recombination (HR), however HR is not error free and can result in detrimental genetic changes. Because the developing embryo requires tight regulation of gene expression in order to develop properly, we propose that the loss or dysfunction of genes involved in embryonic development through aberrant HR may ultimately cause NTDs. To determine if VPA induces HR, CHO 3--6 cells, containing a neomycin (neo) direct repeat recombination substrate, were exposed to VPA for 4 or 24 hours. (Abstract shortened by UMI.)... |
