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

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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.