Diminished or inversed dose-rate effect on clonogenic ability in Ku-deficient rodent cells.
Diminished or inversed dose-rate effect on clonogenic ability in Ku-deficient rodent cells.
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DOI：
10.1093/jrr/rraa128
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发表时间：
2021-03-10
影响因子：
2
通讯作者：
Matsumoto Y
中科院分区：
文献类型：
--
作者：
Tsuchiya H;Shimada M;Tsukada K;Meng Q;Kobayashi J;Matsumoto Y
电离辐射的生物效应，特别是X射线和γ射线等稀疏电离辐射的生物效应，一般会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辐射过程中DNA损伤的修复，但剂量率效应的确切机制仍有待澄清。Ku 70、Ku 86和DNA依赖性蛋白激酶催化亚基（DNA-PKcs）被认为是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，我们测量了Ku 70-，Ku 86-或DNA-PKcs-缺陷啮齿动物细胞的克隆形成能力，与各自的对照细胞平行，对高剂量率（HDR）和低剂量率（LDR）γ射线辐射（~0.9和~1 mGy/min，分别）。对照细胞和小鼠胚胎成纤维细胞（MEF）从一个严重的联合免疫缺陷（scid）小鼠，这是DNA-PKcs缺陷，表现出更高的细胞存活率低剂量照射后比HDR照射后，在相同的剂量。另一方面，来自Ku 70 −/−小鼠的MEF在LDR照射后表现出比HDR照射后更低的克隆形成细胞存活率。Ku 86缺陷的XR-V 15 B和xrs-5细胞在LDR和HDR照射后表现出几乎相同的克隆形成细胞存活。因此，剂量率效应的克隆形成细胞的生存减少，甚至逆转Ku缺陷啮齿动物细胞。这些观察结果表明Ku参与剂量率效应。
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.
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影响因子：
5.3
作者：
Singleton, BK;Priestley, A;Jeggo, PA
通讯作者：
Jeggo, PA
影响因子：
14.9
作者：
Chaung, WR;Mi, LJ;Boorstein, RJ
通讯作者：
Boorstein, RJ
影响因子：
--
作者：
Ruehm, W.;Azizova, T. V.;Woloschak, G. E.
通讯作者：
Woloschak, G. E.
影响因子：
2.6
作者：
Liu, Min;Lee, Solah;Wang, Ya
通讯作者：
Wang, Ya
DOI：
10.1084/jem.186.6.921
发表时间：
1997-09-15
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Ouyang H;Nussenzweig A;Kurimasa A;Soares VC;Li X;Cordon-Cardo C;Li Wh;Cheong N;Nussenzweig M;Iliakis G;Chen DJ;Li GC
通讯作者：
Li GC