Effect of repair gene inhibitor with radiation on tumor cells

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We have studied the function of ATM and NBS1 on the repair of radiation-induced DNA damage by using the technique of premature chromosome condensation (PCC) and the fluorescence in situ hybridization (FISH). It is known that both ATM and NBS1 have important roles on cell cycle checkpoint control and, due to the lack of this function, AT and NBS1 deficient cells are thought to be hyper-sensitive to ionizing radiation. It is also demonstrated that AT and NBS1 cells are very radio-sensitive under non-growing G0 phase. To understand this mechanism we have studied chromosome aberrations under G0 and G1 conditions. The cells we used are normal human fibroblast cells, ATM deficient cells, NBS1 deficient cells and human osteosarcoma cells. When non growing cells were irradiated and either allowed to repair or subculture immediately after irradiation, it was found that normal fibroblast cells, NBS1 cells and tumor cells showed higher survival rate compared to immediate plating condition. To stu … More dy the efficiency and the fidelity of repair, PCC and FISH technique were applied on G0 and G1 cells. The normal fibroblast cells and tumor cells showed much higher fidelity under G0 condition compared to G1 growing condition, whereas AT cells show similar low fidelity of repair under each cell growth condition. NBS1 cells showed more fidelity under G0 condition but less accurate than normal cells. Similar phenomena like AT cells were observed in normal cells when cells when cells were pretreated with ATM inhibitor. Since G1 and G0 cells repair double strand breaks through non-homologous end joining, ATM seems to have function of repair fidelity of NHEJ. We have studied the effect of heavy ion beams on PLDR. It was found that even normal cells showed similar inaccurate fidelity of repair between G0 and G1 repair. It shows that high-LET induced DNA damage can not be accurately repaired even under G0 condition. ATM and NBS1 inhibition of G0 tumor cells may result in more tumor cell death. Further studies using mice are undergoing. Less