Abstract：Objective To investigate the radiobiological effects of radiation with different dose rates on human nasopharyngeal carcinoma cell line CNE-2 treated with or without a poly ADP-ribose polymerase (PARP) inhibitor,olaparib. Methods The concentration of olaparib used to treat cells equaled to the inhibition concentration IC10 of olaparib to CNE-2 cells. The CNE-2 cells were divided into acute radiotherapy (RT) group,fractionated radiotherapy (FRT) group,olaparib+RT group,and olaparib+FRT group. All groups were exposed to radiation of 0,1,2,3,5,7,and 10 Gy at a dose rate of 3 Gy/min.The delivery time for each dose point was 4 min in RT and 30 min in FRT.The colony forming assay was used to evaluate the survival of CNE-2 cells at each dose point. The multi-target,single-hit model was used to fit the cell survival curves and the parameters,D0,Dq,and SF2,were calculated. At dose points of 0,1,and 2 Gy,western blot was used to determine the expression of PARP-1 in the RT group and the FRT group and γH2AX in each group. Immunofluorescence was used to evaluate the γH2AX focus formation. A single factor analysis of variance was used to compare the 4 groups,and two two compared with SNK-q test. Results The IC10 value of olaparib to CNE-2 cells was4.0μmol/L.At dose points of 1 and 2 Gy,the PARP-1 expression was significantly higher in the FRT group than in the RT group (P=0.029,0.022),while the γH2AX focus number was significantly smaller in the FRT group than in the other three groups (all P<0.05);compared with the RT group,the D0,Dq,and SF2 values in the FRT group were increased by 11.67%,15.78%,and 23.61%,respectively;compared with the FRT group,the D0,Dq,and SF2 values in the Olaparib+FRT group decreased by 11.19%,6.44%,and 13.26%,respectively;there were no significant differences in above indices between the RT group,the Olaparib+RT group,and the Olaparib+FRT group. Conclusions For the same radiation dose,fractionation reduces the relative dose rate and weakens the radiobiological effects.low-dose olaparib can compromise the single strand break repair induced by the decline of the relative dose rate in a fractionated irradiation mode,which promotes the formation of double-strand break and improves the radiobiological effects.
Zhao Gang,Huang Xiu,Zheng Taihao et al. Radiobiological effects of irradiation plus olaparib with different dose rates on CNE-2 cell line[J]. Chinese Journal of Radiation Oncology, 2016, 25(7): 764-769.
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