Repair pathways for radiation DNA damage under normoxic and hypoxic conditions: Assessment with a panel of repair-deficient human TK6 cells
Repair pathways for radiation DNA damage under normoxic and hypoxic conditions: Assessment with a panel of repair-deficient human TK6 cells
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常氧和低氧条件下辐射 DNA 损伤的修复途径：用一组修复缺陷的人类 TK6 细胞进行评估
DOI：
10.1093/jrr/rrab084
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发表时间：
2021
影响因子：
2
通讯作者：
Ide Hiroshi
中科院分区：
文献类型：
--
作者：
Tsuda Masataka;Shimizu Naoto;Tomikawa Hinako;Morozumi Ryosuke;Ide Hiroshi
当细胞暴露于电离辐射（IR）时，会产生各种类型的DNA损伤。氧浓度影响IR诱导的DNA损伤的类型和产量。因此，不同的DNA修复机制可能参与了常氧和缺氧细胞对IR照射的反应。然而，常氧与缺氧条件下IR诱导的DNA损伤的修复机制之间的差异尚未澄清。阐明单个修复因子对细胞存活的相对贡献将使我们深入了解在辐射常氧和缺氧细胞中的修复机制。在本研究中，我们使用了一组修复缺陷的人TK6细胞系，涵盖了七个修复途径。在常氧和低氧条件下用X射线照射细胞，并测定每种突变体相对于野生型对常氧和低氧条件的敏感性（即相对敏感性）。细胞的敏感性根据修复缺陷的类型而变化。然而，对于每个修复突变体，在常氧条件下的相对灵敏度与在缺氧条件下的相对灵敏度相当。这一结果表明，个别修复途径的细胞存活的相对贡献是可比的常氧和缺氧的细胞，虽然光谱的IR诱导的DNA损伤在缺氧的细胞不同于常氧的细胞。
Various types of DNA lesions are produced when cells are exposed to ionizing radiation (IR). The type and yield of IR-induced DNA damage is influenced by the oxygen concentration. Thus, different DNA repair mechanisms may be involved in the response of normoxic and hypoxic cells to irradiation with IR. However, differences between the repair mechanisms of IR-induced DNA damage under normoxic versus hypoxic conditions have not been clarified. Elucidating the relative contribution of individual repair factors to cell survival would give insight into the repair mechanisms operating in irradiated normoxic and hypoxic cells. In the present study, we used a panel of repair-deficient human TK6 cell lines that covered seven repair pathways. Cells were irradiated with X-rays under normoxic and hypoxic conditions, and the sensitivities of each mutant relative to thewild-type(i.e. relative sensitivity) were determined for normoxic and hypoxic conditions. The sensitivity of cells varied depending on the type of repair defects. However, for each repair mutant, the relative sensitivity under normoxic conditions was comparable to that under hypoxic conditions. This result indicates that the relative contribution of individual repair pathways to cell survival is comparable in normoxic and hypoxic cells, although the spectrum of IR-induced DNA damage in hypoxic cells differs from that of normoxic cells.