Nakajima Hiroo, Furukawa Chiharu, Chang Young-Chae, Ogata Hiromitsu, Magae Junji
a Department of Breast Surgery, Misugi-kai Sato Hospital, 65-1 Yabuhigashi-machi, Hirakata-shi, Osaka 573-1124, Japan.
b Department of Biotechnology, Institute of Research and Innovation, 1201 Takada, Kashiwa 277-0861, Japan.
Radiat Res. 2017 Aug;188(2):181-190. doi: 10.1667/RR14666.1. Epub 2017 Jun 9.
Biological response to ionizing radiation depends not only on the type of radiation and dose, but also on the duration and dose rate of treatment. For a given radiation dose, the biological response may differ based on duration and dose rate. We studied the properties of two human cell lines, M059K glioma and U2OS osteosarcoma, continuously exposed to γ rays for long time periods of more than five months. Growth inhibition in both cell lines was dependent on total dose when exposed to acute radiation over several minutes, whereas prolonged growth inhibition was dependent on dose rate after continuous irradiation over several months. The minimum dose rate for growth inhibition was 53.6 mGy/h. Cell cycle analysis showed G phase accumulation in cell populations continuously exposed to γ rays, and G phase accumulation in cells acutely exposed to high-dose-rate γ rays. Cells continuously exposed to γ rays continued to exhibit delayed growth suppression even after one month in an environment of background radiation, and maintained a high-level expression of c-Jun and its phosphorylation forms, as well as resistance to apoptosis induced by staurosporine and chemotherapeutic agents. These delayed effects were not observed in cells acutely exposed to 5 Gy of radiation. These results suggest that optimization of the irradiation schedule is crucial for risk estimation, protection and therapeutic utilization of ionizing radiation.
对电离辐射的生物反应不仅取决于辐射类型和剂量，还取决于治疗的持续时间和剂量率。对于给定的辐射剂量，生物反应可能因持续时间和剂量率而异。我们研究了两种人类细胞系，即M059K胶质瘤细胞系和U2OS骨肉瘤细胞系，它们在五个多月的长时间内持续暴露于γ射线。当在几分钟内暴露于急性辐射时，两种细胞系的生长抑制均取决于总剂量，而在连续照射数月后，长期生长抑制则取决于剂量率。生长抑制的最小剂量率为53.6 mGy/h。细胞周期分析显示，持续暴露于γ射线的细胞群体中存在G期积累，急性暴露于高剂量率γ射线的细胞中也存在G期积累。即使在背景辐射环境中放置一个月后，持续暴露于γ射线的细胞仍继续表现出延迟的生长抑制，并维持c-Jun及其磷酸化形式的高水平表达，以及对星形孢菌素和化疗药物诱导的细胞凋亡的抗性。在急性暴露于5 Gy辐射的细胞中未观察到这些延迟效应。这些结果表明，优化照射方案对于电离辐射的风险评估、防护和治疗应用至关重要。
