Analysis of DNA Damage Responses After Boric Acid-mediated Boron Neutron Capture Therapy in Hepatocellular Carcinoma.
BACKGROUND
Boron neutron capture therapy (BNCT) selectively kills tumor cells while sparing adjacent normal cells. Boric acid (BA)-mediated BNCT showed therapeutic efficacy in treating hepatocellular carcinoma (HCC) in vivo. However, DNA damage and corresponding responses induced by BA-mediated BNCT remained unclear. This study aimed to investigate whether BA-mediated BNCT induced DNA double-strand breaks (DSBs) and to explore DNA damage responses in vitro.


MATERIALS AND METHODS
Huh7 Human HCC cells were treated with BA and irradiated with neutrons during BA-BNCT. Cell survival and DNA DSBs were examined by clonogenic assay and expression of phosphorylated H2A histone family member X (γH2AX), respectively. The DNA damage response was explored by determining the expression levels of DNA repair- and apoptosis-associated proteins and conducting a cell-cycle analysis.


RESULTS
DNA DSBs induced by BA-mediated BNCT were primarily repaired through the homologous recombination pathway. BA-mediated BNCT induced G2/M arrest and apoptosis in HCC.


CONCLUSION
Our findings may enable the identification of radiosensitizers or adjuvant drugs for potentiating the therapeutic effectiveness of BA-mediated BNCT for HCC.
['Chen|Kuan-Hao|KH|', 'Lai|Zih-Yin|ZY|', 'Li|Ding-Yu|DY|', 'Lin|Yu-Chuan|YC|', 'Chou|Fong-In|FI|', 'Chuang|Yung-Jen|YJ|']
D051017:Apoptosis Regulatory Proteins D001888:Boric Acids D016754:Boron Neutron Capture Therapy D006528:Carcinoma, Hepatocellular D053148:Caspase 3 D045744:Cell Line, Tumor D002470:Cell Survival D053903:DNA Breaks, Double-Stranded D059766:DNA End-Joining Repair D004260:DNA Repair D004268:DNA-Binding Proteins D004789:Enzyme Activation D006657:Histones D006801:Humans D008113:Liver Neoplasms D011838:Radiation-Sensitizing Agents D059767:Recombinational DNA Repair
DNA damage Hepatocellular carcinoma BNCT DNA repair