摘要目的:对比分析超高剂量率(FLASH)和常规剂量率电子线照射对正常细胞与肿瘤细胞的差异效应。方法:采用6 MeV电子线直线加速器，分别对人肺上皮样细胞株BEAS-2B与肺腺癌细胞株A549进行照射，建立对照(CON)组、常规剂量率(CONV，0.3 Gy/s)照射组和FLASH照射组(200、400 Gy/s)；利用CCK8实验检测不同剂量率照射对正常细胞与肿瘤细胞存活能力的影响；检测照射后细胞超氧化物歧化酶(SOD)和丙二醛(MDA)的含量确定氧化损伤；免疫荧光实验检测细胞DNA双链断裂与修复；流式细胞术进行细胞周期检测。结果:CONV和FLASH照射6、15 Gy后，FLASH组BEAS-2B细胞存活率显著高于CONV组( t＝5.17~7.58， P<0.05)，且BEAS-2B存活率高于A549细胞( t＝3.63~7.79， P<0.05)；CONV照射后，BEAS-2B和A549细胞SOD活力( tBEAS-2B＝2.90~10.39， P<0.05； tA549＝8.96~10.76， P<0.05)和MDA含量( tBEAS-2B＝8.69~11.94， P<0.05； tA549＝10.44~14.08， P<0.05)显著改变；FLASH照射后BEAS-2B细胞SOD活力变化较小，与CON相比差异无统计学意义( P>0.05)，FLASH组A549细胞SOD活力与CONV照射组相比差异无统计学意义( P>0.05)；与CONV照射组相比，FLASH照射组BEAS-2B细胞MDA含量低( t＝6.21~10.12， P<0.05)，A549细胞MDA的含量无明显差异( P>0.05)。与CONV相比，FLASH照射后BEAS-2B细胞出现24~72 h的G 2期稳定阻滞，而A549细胞在照后4 h出现G 1期高比例，但72 h时细胞周期紊乱；照后4 h，FLASH组相比CONV组BEAS-2B细胞γ-H2AX焦点形成较少，且照后24 h γ-H2AX焦点明显减少，FLASH照射后DNA双链断裂较少且修复较快。 结论:FLASH照射后肺上皮样细胞BEAS-2B在存活、氧化损伤、细胞周期和DNA损伤修复方面的辐射损伤相比CONV照射较少，而A549细胞受FLASH照射后的辐射损伤与CONV照射基本一致。

abstractsObjective:To compare the differential effects of FLASH and conventional dose rate (CONV, 0.3 Gy/s) electron beam irradiation on normal and tumor cells.Methods:Using a 6 MeV electron beam linear accelerator, BEAS-2B and A549 were irradiated separately to establish a control group, CONV group, and FLASH group. Using CCK8 experiment to detect the effects of different dose rates of irradiation on the survival ability of normal cells and tumor cells. The oxidative damage was determined by measuring the levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in cells after irradiation; Immunofluorescence assay was used to detect double stranded DNA breaks and repair in cells, while flow cytometry was used for cell cycle detection.Results:After irradiation with CONV and FLASH at 6 and 15 Gy, the survival rate of BEAS-2B cells in the FLASH group was significantly increased compared to the CONV group ( t=5.17-7.58, P<0.05). And as a normal cell, the survival rate of BEAS-2B is higher than that of A549 cells ( t=3.63-7.79, P<0.05). After CONV irradiation, the SOD activity ( tBEAS-2B=2.90-10.39, P<0.05; tA549=8.96-10.76, P<0.05) and MDA content ( tBEAS-2B=8.69-11.94, P<0.05; tA549=10.44-14.08, P<0.05) of BEAS-2B and A549 cells were significantly altered. After FLASH irradiation, there was little change in SOD activity in BEAS-2B cells, and the difference was not statistically significant compared with CON ( P>0.05). There was no statistically significant difference in SOD activity between the FLASH group and the CONV group in A549 cells ( P>0.05). The MDA content of BEAS-2B cells in FLASH group was lower than that in CONV group ( t=6.21-10.12, P<0.05); Compared with the CONV group, there was no significant difference in MDA content in A549 after FLASH irradiation. Compared with CONV, after FLASH irradiation, BEAS-2B cells showed stable G 2 phase arrest at 24-72 h, while A549 cells showed a high proportion of G 1 phase arrest at 4 h, but cell cycle collapsed at 72 h. At 4 h after irradiation, the FLASH group showed less formation of gamma H2AX foci in BEAS-2B cells compared to the CONV group, and the γ-H2AX foci significantly decreased after 24 h. After FLASH irradiation, in DNA double-strand breaks was reduced the number, and then were repaired more quickly. Conclusions:After FLASH irradiation, the radiation damage to lung epithelial-like cells BEAS-2B in terms of survival, oxidative damage, cell cycle, and DNA damage repair is less than that of CONV irradiation, the radiation damage of A549 cells after FLASH irradiation is bascally consistent with that after CONV irradiation.