Alpha particle-induced bystander eff ect is mediated by ROS via a p53-dependent SCO2 pathway in hepatoma cells
Alpha particle-induced bystander eff ect is mediated by ROS via a p53-dependent SCO2 pathway in hepatoma cells
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DOI：
10.3109/09553002.2013.817706
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发表时间：
2013-12-01
影响因子：
2.6
通讯作者：
Shao, Chunlin
中科院分区：
文献类型：
--
作者：
Li, Jitao;He, Mingyuan;Shao, Chunlin
目的：辐射诱导的旁观者效应（里贝）对放射治疗的效率有重要意义，但细胞代谢的潜在作用是广泛未知的。目前在肝细胞共培养系统中研究了细胞色素c氧化酶2（SCO 2）（呼吸链的关键效应物）和相关信号传导因子的合成在α粒子诱导的旁观者损伤中的作用。材料和方法：人肝癌细胞HepG 2与野生型p53（wtp 53）和Hep 3B用0.4戈伊α粒子照射p53 null细胞，并与未照射的正常肝细胞HL-7702共培养6 h，观察旁观者HL-7702细胞微核（MN）的发生率。检测照射后肝癌细胞总P53、磷酸化P53（p-P53）、SCO 2和活性氧（ROS）的表达。结果：α射线照射后的HepG 2细胞可诱导HL-7702细胞产生旁观者损伤，而α射线照射后的Hep 3B细胞则无此效应，经p53 siRNA、SCO 2 siRNA或DMSO预处理后，这种旁观者效应被减弱。照射后HepG 2细胞p-P53蛋白、SCO 2 mRNA表达、SCO 2蛋白活性及细胞内ROS水平均升高，而Hep 3B细胞则无明显变化，经p53 siRNA处理后p-P53蛋白、SCO 2 mRNA表达、SCO 2蛋白活性及细胞内ROS水平均降低。结论：p53及其下游的SCO 2参与了α粒子照射后肝癌细胞旁观者效应的调节，ROS的产生可能是引发这种旁观者效应的早期事件。
Purpose : The radiation-induced bystander effect (RIBE) has important implications for the efficiency of radiotherapy but the underlying role of cellular metabolism is widely unknown. The roles of synthesis of cytochrome c oxidase 2 (SCO2), a key effector for respiratory chain, and related signaling factors in alpha-particle-induced bystander damage were currently investigated in a liver cell co-culture system.Materials and methods : Human hepatoma cells of HepG2 with wild-type p53 (wtp53) and Hep3B (p53 null) were irradiated with 0.4 Gy of alpha-particles and co-cultured with non-irradiated normal liver cells HL-7702 for 6 h, then the incidence of micronucleus (MN) in the bystander HL-7702 cells was analyzed. The expressions of total P53, phospho-P53 (p-P53), SCO2, and reactive oxygen species (ROS) in the irradiated hepatoma cells were detected. In some experiments, the hepatoma cells were respectively treated with p53 siRNA, SCO2 siRNA, or dimethyl sulfoxide (DMSO) before irradiation.Results : Bystander damage in HL-7702 cells was induced by alpha-irradiated HepG2 cells but not by alpha-irradiated Hep3B cells, and this bystander effect was diminished when the irradiated HepG2 cells were pretreated with p53 siRNA, SCO2 siRNA, or DMSO. Meanwhile, the expressions of p-P53 protein and SCO2 mRNA, the activity of SCO2 protein, and intracellular ROS were all increased in the irradiated HepG2 cells but not Hep3B cells and these expressions were eliminated by p53 siRNA treatment. Moreover, the radiation-enhanced expressions of SCO2 and ROS were inhibited by SCO2 siRNA.Conclusion : alpha-particle-induced bystander effect was regulated by p53 and its downstream SCO2 in the irradiated hepatoma cells, and ROS generation could be an early event for triggering this bystander response.