Up-regulation of ROS by mitochondria-dependent bystander signaling contributes to genotoxicity of bystander effects
Up-regulation of ROS by mitochondria-dependent bystander signaling contributes to genotoxicity of bystander effects
复制标题
线粒体依赖性旁观者信号传导上调 ROS 有助于旁观者效应的遗传毒性
DOI：
10.1016/j.mrfmmm.2009.04.006
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发表时间：
2009-06-18
影响因子：
2.3
通讯作者：
Wu, Lijun
中科院分区：
文献类型：
--
作者：
Chen, Shaopeng;Zhao, Ye;Wu, Lijun
在旁观者细胞中可以观察到基因组的不稳定性。然而，潜在的机制仍然相对不清楚。在之前的一项研究中，我们发现受辐射的细胞释放线粒体依赖性细胞内因子，这可能导致旁观者 γ-H2AX 诱导。在本文中，我们使用正常（rho（+））和线粒体DNA耗尽（rho（0））人仓鼠杂交细胞，通过培养基转移实验研究线粒体对旁观者效应中遗传毒性的影响。通过用γ-H2AX检测DNA双链断裂，我们发现在收获辐照条件细胞培养基（ICCM）时，γ-H2AX阳性细胞的比例随时间变化。与rho(0) ICCM10min相比，在照射后10分钟(rho(+) ICCM10min)从受照射的rho(+)细胞收获的ICCM引起旁观者gamma-H2AX诱导的更大增加，而rho(0) ICCM10min仅导致旁观者gamma-H2AX诱导的轻微增加。 rho(+) ICCM10min 还可导致 ROS 产生上调（10 分钟增加 35%），而用 rho(0) ICCM10min 处理的细胞则没有显着增加。我们用 ROS 清除剂二甲亚砜 (DMSO) 处理细胞，并通过 rho(+) ICCM 猝灭 γ-H2AX 诱导。此外，在转移培养基并连续培养7天后，我们发现rho(+) ICCM处理的旁观者细胞的后代中CD59(-)基因位点突变显着增加(增加了45.9%)并且细胞死亡延迟。总之，这里介绍的工作表明，线粒体依赖性 ROS 的上调可能对于介导旁观者效应的遗传毒性非常重要。 (c) 2009 Elsevier B.V. 保留所有权利。
Genomic instability can be observed in bystander cells. However, the underlying mechanism(s) is still relatively unclear. In a previous study, we found that irradiated cells released mitochondria-dependent intracellular factor(s) which could lead to bystander gamma-H2AX induction. In this paper, we used normal (rho(+)) and mtDNA-depleted (rho(0)) human-hamster hybrid cells to investigate mitochondrial effects on the genotoxicity in bystander effect through medium transfer experiments. Through the detection of DNA double-strand breaks with gamma-H2AX, we found that the fraction of gamma-H2AX positive cells changed with time when irradiation conditioned cell medium (ICCM) were harvested. ICCM harvested from irradiated rho(+) cells at 10 min post-irradiation (rho(+) ICCM10min) caused larger increases of bystander gamma-H2AX induction comparing to rho(0) ICCM10min, which only caused a slight increase of bystander gamma-H2AX induction. The rho(+) ICCM10min could also result in the up-regulation of ROS production (increased by 35% at 10 min), while there was no significant increase in cells treated with rho(0) ICCM10min. We treated cells with dimethyl sulfoxide (DMSO), the scavenger of ROS, and quenched gamma-H2AX induction by rho(+) ICCM. Furthermore, after the medium had been transferred and the cells were continuously cultured for 7 days, we found significantly increased CD59(-) gene loci mutation (increased by 45.9%) and delayed cell death in the progeny of rho(+) ICCM-treated bystander cells. In conclusion, the work presented here suggested that upregulation of the mitochondria-de pendent ROS might be very important in mediating genotoxicity of bystander effects. (c) 2009 Elsevier B.V. All rights reserved.