持续低剂量率辐射下HepG_2细胞辐射敏感性与ATM磷酸化的关系  

Relationship of HepG_2 cell sensitivity to continuous low dose-rate irradiation with ataxia-telangiectasia mutated phosphorylation

作　　者：梅雀林[1] 杨建勇[1] 杜端明[2] 陈在中[2] 刘鹏程[2] 

机构地区：[1]中山大学第一附属医院 [2]北京大学深圳医院影像中心,广东深圳518036

出　　处：《南方医科大学学报》2007年第9期1391-1395,共5页Journal of Southern Medical University

基　　金：吴阶平医学科研基金(320.6720.0501);深圳市科技计划项目(200404093)

摘　　要：目的探讨持续低剂量率辐射下HepG2细胞ATM磷酸化的变化及其对HepG2细胞增殖活性的影响。方法体外培养的HepG2细胞分别接受持续低剂量率(7.76cGy/h)和高剂量率(4500cGy/h)电离辐射,比较同等剂量下低剂量率和高剂量率辐射后HepG2细胞ATM磷酸化程度和细胞存活分数。结果无论给予低剂量率或高剂量率照射,HepG2细胞接受0.5Gy的电离辐射时,ATM蛋白均可达到最大的磷酸化。随着辐射剂量的增加,在持续低剂量率辐射下,HepG2细胞ATM磷酸化蛋白表达逐渐减弱;而在高剂量率辐射下,ATM磷酸化蛋白稳定不变。当高、低剂量率辐射诱导产生的ATM磷酸化程度相当时,两者的存活分数无明显差异(P>0.05);当持续低剂量率辐射组ATM磷酸化蛋白表达明显弱于高剂量率辐射组时,HepG2细胞的存活分数显著低于高剂量率辐射组(P<0.01)。结论持续低剂量率辐射增加了HepG2细胞的辐射敏感性,其机制与持续低剂量率辐射下部分ATM磷酸化蛋白失活有关。抑制ATM磷酸化,可以增加HepG2肝癌细胞的辐射敏感性。Objective To investigate the changes ofataxia-telangiectasia mutated （ATM） phosphorylation irl HepG2 cells in relation to HepG2 cell survival under continuous low dose-rate irradiation. Methods HepG2 cells were exposed to equivalent irradiation doses delivered at either a continuous low dose-rate （7.76 cGy/h） or a high dose-rate （4500 cGy/h）, and the phosphorylated ATM proteins and surviving fraction of HepG2 cells after the exposures were compared. Results The phosphorylation of ATM protein was maximal at 0.5 Gy irradiation delivered at either a high doserate or a continuous low doserate. As the radiation dose increased, ATM protein phosphorylation decreased under continuous low dose-rate irradiation, but remained stable under high dose-rate irradiation. With comparable ATM protein phosphorylation induced by continuous low dose-rate irradiation and high dose-rate irradiation, there was no significant difference in the surviving fraction of HepG2 cells （P〉0.05）, but at a significantly lower ATM protein phosphorylation level than that induced by high dose-rate irradiation, continuous low dose-rate irradiation resulted in increased cell killing （P〈0.01）. Conclusion Continuous low dose-rate irradiation increases HepG2 cells radiosensitivity as compared with high dose-rate irradiation. Increased cell killing following continuous low dose-rate irradiation is associated with reduced phosphorylated ATM protein, and inhibition of ATM phosphorylation may increase the radiosensitivity of HepG2 cells.

关 键 词：Γ-辐射 肝肿瘤 HEPG2细胞 辐射敏感性 共济失调毛细血管扩张症突变基因 

分 类 号：R73-3[医药卫生—肿瘤]