ABSTRACT

Objectives: High dose-rate ionizing radiation (IR) causes severe DSB damage, as well as reactive oxygen species (ROS) accumulation and oxidative stress. However, it is unknown what biological processes are affected by low dose-rate IR; therefore, the molecular relationships between mitochondria changes and oxidative stress in human normal cells was investigated after low dose-rate IR.

Methods: We compared several cellular response between high and low dose-rate irradiation using cell survival assay, ROS/RNS assay, immunofluorescence and western blot analysis.

Results: Reduced DSB damage and increased levels of ROS, with subsequent oxidative stress responses, were observed in normal cells after low dose-rate IR. Low dose-rate IR caused several mitochondrial changes, including morphology mass, and mitochondrial membrane potential, suggesting that mitochondrial damage was caused. Although damaged mitochondria were removed by mitophagy to stop ROS leakage, the mitophagy-regulatory factor, PINK1, was reduced following low dose-rate IR. Although mitochondrial dynamics (fission/fusion events) are important for the proper mitophagy process, some mitochondrial fusion factors decreased following low dose-rate IR.

Discussion: The dysfunction of mitophagy pathway under low dose-rate IR increased ROS and the subsequent activation of the oxidative stress response.

 抽象的

目的：高剂量率电离辐射 (IR) 会导致严重的 DSB 损伤，以及活性氧 (ROS) 积累和氧化应激。然而，尚不清楚哪些生物过程会受到低剂量率红外的影响；因此，我们研究了低剂量率IR后线粒体变化与人类正常细胞氧化应激之间的分子关系。

方法：我们使用细胞存活测定、ROS/RNS 测定、免疫荧光和蛋白质印迹分析比较了高剂量率和低剂量率照射之间的几种细胞反应。

结果：低剂量率 IR 后，在正常细胞中观察到 DSB 损伤减少、ROS 水平增加，以及随后的氧化应激反应。低剂量率IR引起了一些线粒体变化，包括形态质量和线粒体膜电位，表明引起了线粒体损伤。尽管通过线粒体自噬去除了受损的线粒体以阻止 ROS 泄漏，但低剂量率 IR 后线粒体自噬调节因子 PINK1 减少。尽管线粒体动力学（裂变/融合事件）对于适当的线粒体自噬过程很重要，但低剂量率 IR 后一些线粒体融合因子会减少。

讨论：低剂量IR下线粒体自噬途径的功能障碍增加了ROS并随后激活了氧化应激反应。