Laboratory for Zero-Carbon Energy, Institute of Innovative Research, Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro-ku, Tokyo 152-8550, Japan.
Department of Interdisciplinary Environment, Graduate School of Human and Environmental Sciences, Kyoto University, Yoshidanihonmatsucho, Sakyo-ku, Kyoto 606-8501, Japan.
Radiat Prot Dosimetry. 2022 Sep 9;198(13-15):990-997. doi: 10.1093/rpd/ncac030.
It is generally and widely accepted that the biological effects of a given dose of ionizing radiation, especially those of low linear energy transfer radiations like X-ray and gamma ray, become smaller as the dose rate becomes lower. This phenomenon, known as 'dose-rate effect (DRE),' is considered due to the repair of sublethal damage during irradiation but the precise mechanisms for DRE have remained to be clarified. We recently showed that DRE in terms of clonogenic cell survival is diminished or even inversed in rodent cells lacking Ku, which is one of the essential factors in the repair of DNA double-strand breaks (DSBs) through non-homologous end joining (NHEJ). Here we review and discuss the involvement of NHEJ in DRE, which has potential implications in radiological protection and cancer therapeutics.
一般和广泛认为，给定剂量的电离辐射的生物效应，特别是像 X 射线和伽马射线这样低线性能量转移辐射的生物效应，随着剂量率的降低而变小。这种现象被称为“剂量率效应（DRE）”，被认为是由于在照射过程中修复亚致死损伤所致，但 DRE 的精确机制仍有待阐明。我们最近表明，在缺乏 Ku 的啮齿动物细胞中，克隆形成细胞存活方面的 DRE 减少甚至逆转，Ku 是通过非同源末端连接（NHEJ）修复 DNA 双链断裂（DSBs）的必需因素之一。在这里，我们回顾和讨论了 NHEJ 在 DRE 中的作用，这对放射防护和癌症治疗具有潜在意义。
