Characterization of valproic acid‐initiated homologous recombination

摘要: BACKGROUND: Valproic acid (VPA) is a frequently used antiepileptic agent and known teratogen. Previous research suggests that inhibition of histone deacetylases (HDACs) may play role in VPA-induced teratogenicity. We have also shown VPA exposure leads to both an increase reactive oxygen species (ROS) production increased frequency homologous recombination (HR). METHODS: In the present study, we evaluated HDAC VPA-initiated HR determine if could alter repair activity and/or cause DNA double-strand breaks (DSBs), which would then initiate repair. Histone acetylation status was assessed led CHO 33 cells. RESULTS: Our results demonstrate (5 mM) acetylated H3 H4 protein levels after 10 24 hr. Secondly, our assay where artificial DSB induced cells assess activity, did not affect HR. Subsequently, susceptibility DSBs, number γ-H2AX foci using immunocytochemistry revealed 10- 24-hr VPA. CONCLUSIONS: Although demonstrated protective effect polyethylene glycol-catalase against generation intracellular ROS within 24 hr, observed oxidation. These studies suggest signaling roles maintenance cell-cycle arrest initiating damage Birth Defects Res (Part B) 89:124–132, 2010. © 2010 Wiley-Liss, Inc.