Inhibition of radiation-induced DNA dsbs repair by inducing misrejoining and its clinical application

众所周知，在肿瘤中存在一些低氧细胞，这些细胞对辐射具有抵抗力。这些细胞也被称为静止细胞，其细胞周期属于G0。我们测定了细胞在低氧和常氧条件下的敏感性。研究发现，当细胞在每种条件下修复几个小时时，细胞存活率几乎相同，这表明低氧细胞可以修复DSB，其效率与正常氧细胞相同。为了增强辐射效应，我们使用了Ku80 siRNA for小鼠(Balb/c)肿瘤，并在实验前移植，发现使用它可以抑制肿瘤的生长。然而，当小鼠肿瘤在低氧条件下通过血流排出注射Ku80 siRNA时，与正常氧条件下相比没有显著差异。这一结果表明Ku80 siRNA本身对缺氧静止细胞不起作用。由于大多数静止细胞使用非同源末端连接(NHEJ)修复过程修复DSB，因此使用其他NHEJ(非同源末端连接)抑制剂来增强肿瘤的放射敏感性的进一步实验正在进行中。

It is known that in tumors there are some fraction of hypoxic cells and these cells are resistant to radiation. These cells are also known as quiescent cells which cell cycle belongs to G0. We have measured the cell sensitivity under hypoxic and normal oxic condition. It was found that when cells are allowed to repair for several hours under each condition, cell survival was almost the same, suggesting that hypoxic cells can repair dsbs as efficiency as normal oxic cells. To enhance radiation effect, we employed Ku80 siRNA for mice (Balb/c) tumors, which were transplanted before experiment, and found that tumor growth was suppressed by using it. However, when mice tumors were injected with Ku80 siRNA under hypoxic condition by expulsion of blood flow, no significant difference was observed compared to normal oxic condition. This result suggests that Ku80 siRNA itself is not effective to hypoxic quiescent cells. Further experiments are underway using other NHEJ (non homologous end joining) inhibitors to enhance tumor radiosensitivity since most quiescent cells repair dsbs using NHEJ repair process.