{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T17:40:27Z","timestamp":1760204427794},"reference-count":44,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2010,3,31]],"date-time":"2010-03-31T00:00:00Z","timestamp":1269993600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Birth Defects Research Pt B"],"published-print":{"date-parts":[[2010,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:bold>BACKGROUND<\/jats:bold>: Valproic acid (VPA) is a frequently used antiepileptic agent and known teratogen. Previous research suggests that inhibition of histone deacetylases (HDACs) may play a role in VPA\u2010induced teratogenicity. We have also shown that VPA exposure leads to both an increase in reactive oxygen species (ROS) production and increased frequency of homologous recombination (HR). <jats:bold>METHODS<\/jats:bold>: In the present study, we evaluated the role of HDAC inhibition in VPA\u2010initiated HR to determine if HDAC inhibition could alter repair activity and\/or cause DNA double\u2010strand breaks (DSBs), which would then initiate repair. Histone acetylation status was assessed to determine if VPA exposure led to HDAC inhibition in CHO 33 cells. <jats:bold>RESULTS<\/jats:bold>: Our results demonstrate that VPA (5\u2009mM) exposure leads to increased acetylated histone H3 and H4 protein levels after 10 to 24\u2009hr. Secondly, in our recombination assay where an artificial DNA DSB was induced in CHO 33 cells to assess repair activity, VPA exposure did not affect the repair activity of VPA\u2010initiated HR. Subsequently, to determine if VPA could increase susceptibility to DNA DSBs, the number of \u03b3\u2010H2AX foci was assessed using immunocytochemistry and results revealed an increase in \u03b3\u2010H2AX foci after 10\u2010 to 24\u2010hr exposure to VPA. <jats:bold>CONCLUSIONS<\/jats:bold>: Although we demonstrated the protective effect of polyethylene glycol\u2010catalase against VPA\u2010induced HR and the generation of intracellular ROS within 24\u2009hr, we did not observed an increase in DNA oxidation. These studies suggest that HDAC inhibition and ROS signaling may play roles in DNA maintenance and cell\u2010cycle arrest in initiating DNA damage and repair. <jats:italic>Birth Defects Res (Part B)<\/jats:italic> 89:124\u2013132, 2010. \u00a9 2010 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/bdrb.20236","type":"journal-article","created":{"date-parts":[[2010,3,31]],"date-time":"2010-03-31T14:56:59Z","timestamp":1270047419000},"page":"124-132","source":"Crossref","is-referenced-by-count":15,"title":["Characterization of valproic acid\u2010initiated homologous recombination"],"prefix":"10.1002","volume":"89","author":[{"given":"Kevin","family":"Sha","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Louise 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