Department of Radiation Oncology, Emory University School of Medicine, Winship Cancer Institute of Emory University, Atlanta, Georgia 30322, USA.
J Cell Physiol. 2011 Feb;226(2):369-74. doi: 10.1002/jcp.22342.
Low-dose (≤0.1 Gy) radiation-induced adaptive responses could protect cells from high-challenge dose radiation-induced killing. The protective role is believed to promote the repair of DNA double-strand breaks (DSBs) that are a severe threat to cell survival. However, it remains unclear which repair pathway, homologous recombination repair (HRR) or non-homologous end-joining (NHEJ), is promoted by low-dose radiation. To address this question, we examined the effects of low-dose (0.1 Gy) on high-challenge dose (2-4 Gy) induced killing in NHEJ- or HRR-deficient cell lines. We showed that 0.1 Gy reduced the high-dose radiation-induced killing for wild-type or HRR-deficient cells, but enhanced the killing for NHEJ-deficient cells. Interestingly, low-dose radiation also enhanced the killing for wild-type cells exposed to high-challenge dose radiation with high-linear energy transfer (LET). Because it is known that high-LET radiation induces an inefficient NHEJ, these results support that the low-dose radiation-stimulated protective role in reducing high-challenge dose (low-LET)-induced cell killing might depend on NHEJ. In addition, we showed that low-dose radiation activated the DNA-PK catalytic subunit (DNA-PKcs) and the inhibitor of DNA-PKcs destroyed the low-dose radiation-induced protective role. These results suggest that low-dose radiation might promote NHEJ through the stimulation of DNA-PKcs activity and; therefore, increase the resistance of cells to high-challenge dose radiation-induced killing.
低剂量（≤0.1Gy）辐射诱导的适应性反应可以保护细胞免受高挑战剂量辐射诱导的杀伤。这种保护作用被认为可以促进修复对细胞存活构成严重威胁的 DNA 双链断裂（DSBs）。然而，低剂量辐射促进哪种修复途径（同源重组修复（HRR）或非同源末端连接（NHEJ））尚不清楚。为了解决这个问题，我们研究了低剂量（0.1Gy）对 NHEJ 或 HRR 缺陷细胞系中高挑战剂量（2-4Gy）诱导杀伤的影响。我们表明，0.1Gy 降低了野生型或 HRR 缺陷细胞的高剂量辐射诱导杀伤，但增强了 NHEJ 缺陷细胞的杀伤。有趣的是，低剂量辐射也增强了高挑战剂量（低 LET）辐射暴露的野生型细胞的杀伤。因为众所周知，高 LET 辐射诱导低效的 NHEJ，这些结果支持低剂量辐射刺激的减少高挑战剂量（低 LET）诱导细胞杀伤的保护作用可能依赖于 NHEJ。此外，我们表明低剂量辐射激活了 DNA-PK 催化亚基（DNA-PKcs），并且 DNA-PKcs 的抑制剂破坏了低剂量辐射诱导的保护作用。这些结果表明，低剂量辐射可能通过刺激 DNA-PKcs 活性来促进 NHEJ，从而增加细胞对高挑战剂量辐射诱导杀伤的抵抗力。
