放射增敏剂
电离辐射
线性能量转移
辐照
PARP抑制剂
癌症研究
DNA修复
质子
相对生物效应
DNA损伤
聚ADP核糖聚合酶
布拉格峰
质子疗法
化学
放射治疗
核医学
放射化学
医学
聚合酶
DNA
物理
生物化学
核物理学
内科学
作者
Takahisa Hirai,Soichiro Saito,Hiroaki Fujimori,K. Matsushita,Teiji Nishio,Ryuichi Okayasu,Mitsuko Masutani
标识
DOI:10.1016/j.bbrc.2016.07.062
摘要
The poly(ADP-ribose) polymerase (PARP)-1 regulates DNA damage responses and promotes base excision repair. PARP inhibitors have been shown to enhance the cytotoxicity of ionizing radiation in various cancer cells and animal models. We have demonstrated that the PARP inhibitor (PARPi) AZD2281 is also an effective radiosensitizer for carbon-ion radiation; thus, we speculated that the PARPi could be applied to a wide therapeutic range of linear energy transfer (LET) radiation as a radiosensitizer. Institutes for biological experiments using proton beam are limited worldwide. This study was performed as a cooperative research at heavy ion medical accelerator in Chiba (HIMAC) in National Institute of Radiological Sciences. HIMAC can generate various ion beams; this enabled us to compare the radiosensitization effect of the PARPi on cells subjected to proton and carbon-ion beams from the same beam line. After physical optimization of proton beam irradiation, the radiosensitization effect of the PARPi was assessed in the human lung cancer cell line, A549, and the pancreatic cancer cell line, MIA PaCa-2. The effect of the PARPi, AZD2281, on radiosensitization to Bragg peak was more significant than that to entrance region. The PARPi increased the number of phosphorylated H2AX (γ-H2AX) foci and enhanced G2/M arrest after proton beam irradiation. This result supports our hypothesis that a PARPi could be applied to a wide therapeutic range of LET radiation by blocking the DNA repair response.
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