Suberoylanilide hydroxamic acid affects γH2AX expression in osteosarcoma, atypical teratoid rhabdoid tumor and normal tissue cell lines after irradiation

摘要: Osteosarcoma and atypical teratoid rhabdoid tumors are tumor entities with varying response to common standard therapy protocols. Histone acetylation affects chromatin structure gene expression which considered influence radiation sensitivity. The aim of this study was investigate the effect combination histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) irradiation on osteosarcoma compared normal tissue cell lines. Clonogenic assay used determine survival. DNA double-strand breaks (DSB) were examined by pulsed-field electrophoresis (PFGE) as well γH2AX immunostaining involving flow cytometry, fluorescence microscopy, immunoblot analysis. SAHA lead an increased radiosensitivity in but not indicator for DSB significantly when applied 24 h before sarcoma cultures. In contrast, lines reduced combined SAHA. Analysis initial fragmentation fragment rejoining PFGE, however, did reveal differences pretreatment either type. increases H2AX phosphorylation status SAHA-treated cells post likely reflects its delayed dephosphorylation within damage signal decay rather than acetylation-dependent overall efficacy induction rejoining. results support hypothesis that combining may provide a promising strategy treatment solid tumors.