Laboratory for Advanced Nuclear 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.
J Radiat Res. 2021 Mar 10;62(2):198-205. doi: 10.1093/jrr/rraa128.
The biological effects of ionizing radiation, especially those of sparsely ionizing radiations like X-ray and γ-ray, are generally reduced as the dose rate is reduced. This phenomenon is known as 'the dose-rate effect'. The dose-rate effect is considered to be due to the repair of DNA damage during irradiation but the precise mechanisms for the dose-rate effect remain to be clarified. Ku70, Ku86 and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) are thought to comprise the sensor for DNA double-strand break (DSB) repair through non-homologous end joining (NHEJ). In this study, we measured the clonogenic ability of Ku70-, Ku86- or DNA-PKcs-deficient rodent cells, in parallel with respective control cells, in response to high dose-rate (HDR) and low dose-rate (LDR) γ-ray radiation (~0.9 and ~1 mGy/min, respectively). Control cells and murine embryonic fibroblasts (MEF) from a severe combined immunodeficiency (scid) mouse, which is DNA-PKcs-deficient, showed higher cell survival after LDR irradiation than after HDR irradiation at the same dose. On the other hand, MEF from Ku70-/- mice exhibited lower clonogenic cell survival after LDR irradiation than after HDR irradiation. XR-V15B and xrs-5 cells, which are Ku86-deficient, exhibited mostly identical clonogenic cell survival after LDR and HDR irradiation. Thus, the dose-rate effect in terms of clonogenic cell survival is diminished or even inversed in Ku-deficient rodent cells. These observations indicate the involvement of Ku in the dose-rate effect.
电离辐射的生物效应，尤其是 X 射线和γ射线等稀疏电离辐射的生物效应，通常随着剂量率的降低而降低。这种现象被称为“剂量率效应”。剂量率效应被认为是由于在照射过程中 DNA 损伤的修复，但剂量率效应的确切机制仍有待阐明。Ku70、Ku86 和 DNA 依赖性蛋白激酶催化亚基（DNA-PKcs）被认为构成了通过非同源末端连接（NHEJ）修复 DNA 双链断裂（DSB）的传感器。在这项研究中，我们平行测量了 Ku70、Ku86 或 DNA-PKcs 缺陷型啮齿动物细胞以及各自的对照细胞对高剂量率（HDR）和低剂量率（LDR）γ射线辐射（分别约为 0.9 和 1 mGy/min）的集落形成能力。对照细胞和严重联合免疫缺陷（scid）小鼠（其 DNA-PKcs 缺陷）的鼠胚胎成纤维细胞（MEF）在 LDR 照射后比 HDR 照射后的细胞存活率更高。另一方面，Ku70-/- 小鼠的 MEF 在 LDR 照射后比 HDR 照射后的集落形成细胞存活率更低。Ku86 缺陷的 XR-V15B 和 xrs-5 细胞在 LDR 和 HDR 照射后表现出相似的集落形成细胞存活率。因此，在 Ku 缺陷型啮齿动物细胞中，集落形成细胞存活率的剂量率效应减弱甚至逆转。这些观察结果表明 Ku 参与了剂量率效应。
