• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of Cellular Physiology >The non-homologous end-joining pathway is not involved in the radiosensitization of mammalian cells by heat shock.
【24h】

The non-homologous end-joining pathway is not involved in the radiosensitization of mammalian cells by heat shock.

机译：的异源end-joining途径不是参与哺乳动物的放射线增减由热休克细胞。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

A synergistic increase in cell killing is observed when a heat-shock is administered prior to, during, or immediately after exposure to ionizing radiation (IR). This phenomenon, known as heat-radiosensitization, is believed to be mediated by inhibition of repair of radiation-induced double strand breaks (DSB) when cells are exposed to temperatures above 42 degrees C. However, the mechanism by which heat inhibits DSB repair is unclear. The bulk of radiation-induced DSBs are repaired via the non-homologous end-joining pathway (NHEJ). Several reports indicate that the Ku70 and Ku80 subunits of the mammalian DNA-dependent protein kinase (DNA-PK), a complex involved in NHEJ, appear to be susceptible to a heat-induced loss of DNA-binding activity, with Ku80 representing the heat-sensitive component. Since the heat-induced loss and subsequent recovery of Ku-DNA binding activity correlates well with heat-radiosensitization, a role for Ku80 and NHEJ in heat-radiosensitization has been proposed. However, direct evidence implicating Ku80 (and NHEJ) in heat-radiosensitization has been indeterminate. In this study, we demonstrate that equitoxic heat treatments at 42.5-45.5 degrees C induce a similar amount of aggregation of Ku80 in human U-1 melanoma cells. These data suggest that the time-temperature-dependent relationship between heat lethality and Ku80 aggregation are similar. However, the aggregation/disaggregation of Ku80 and its transient or permanent inactivation is unrelated to heat-radiosensitization. When survival curves were obtained for irradiated or irradiated and heated Ku80(-/-) mouse embryo fibroblasts (MEFs) and compared with survival curves obtained for wild-type (WT) cells, we found that heat-radiosensitization was not reduced in the Ku80(-/-) cells, but actually increased. Thus, our findings indicate that Ku80 is not essential for heat-radiosensitization. Non-involvement of Ku-dependent or Ku-independent NHEJ pathways in heat-radiosensitization was confirmed by comparing clonogenic survival between DNA ligase IV-defective and WT human cells. Our data therefore implicate homologous recombination in inhibition of repair of radiation-induced DSBs and as a target for heat-radiosensitization.
机译：协同增加细胞杀死当热休克管理之前,期间,或暴露于电离后立即辐射(IR)。heat-radiosensitization,被认为是由抑制修理的辐射诱导双链断裂(双边带)细胞暴露在温度高于42然而,度c .热的机理抑制双边带修复尚不清楚。辐射诱导修复通过双边带异源end-joining通路(NHEJ)。一些报告显示,Ku70 Ku80子单元的哺乳动物依赖dna的蛋白质参与NHEJ激酶(dna - pk),一个复杂的,似乎容易燥热引起的损失dna结合活性,Ku80代表热敏感组件。燥热引起的损失和随后的复苏Ku-DNA绑定活动密切相关、角色Ku80 heat-radiosensitization NHEJ在heat-radiosensitization已提上日程。然而,直接证据暗示Ku80 (在heat-radiosensitization NHEJ)不确定的。equitoxic热处理在42.5 - -45.5摄氏度诱发类似Ku80的聚合人类U-1黑色素瘤细胞。time-temperature-dependent关系热之间的杀伤力和Ku80聚合相似的。Ku80及其临时或永久失活无关heat-radiosensitization。辐照和辐照获得吗加热Ku80(- / -)小鼠胚胎成纤维细胞(mef)并与获得的生存曲线野生型(WT)细胞,我们发现heat-radiosensitization并没有减少Ku80(- / -)细胞,但实际上增加了。我们的发现表明Ku80不是必不可少的heat-radiosensitization。Ku-dependent或Ku-independent NHEJ通路heat-radiosensitization证实了对比单独使用DNA连接酶之间的生存IV-defective和WT人类细胞。因此表明同源重组抑制辐射引发的双边带的修复并为heat-radiosensitization作为目标。

著录项

相似文献

  • 外文文献
  • 中文文献
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号