Research Centre for Medical Genetics, Russian Academy of Medical Sciences, Moscow, Russia.
Mutat Res. 2012 Jan 3;729(1-2):52-60. doi: 10.1016/j.mrfmmm.2011.09.005. Epub 2011 Oct 4.
The development of the bystander effect induced by low doses of irradiation in human umbilical vein endothelial cells (HUVECs) depends on extracellular DNA (ecDNA) signaling pathway. We found that the changes in the levels of ROS and NO production by human endothelial cells are components of the radiation induced bystander effect that can be registered at a low dose. We exposed HUVECs to X-ray radiation and studied effects of ecDNA(R) isolated from the culture media conditioned by the short-term incubation of irradiated cells on intact HUVECs. Effects of ecDNA(R) produced by irradiated cells on ROS and NO production in non-irradiated HUVECs are similar to bystander effect. These effects at least partially depend on TLR9 signaling. We compared the production of the nitric oxide and the ROS in human endothelial cells that were (1) irradiated at a low dose; (2) exposed to the ecDNA(R) extracted from the media conditioned by irradiated cells; and (3) exposed to human DNA oxidized in vitro. We found that the cellular responses to all three stimuli described above are essentially similar. We conclude that irradiation-related oxidation of the ecDNA is an important component of the ecDNA-mediated bystander effect.
低剂量辐射诱导旁观者效应的发展取决于细胞外 DNA（ecDNA）信号通路。我们发现，人内皮细胞中 ROS 和 NO 产生水平的变化是辐射诱导旁观者效应的组成部分，可以在低剂量下检测到。我们用 X 射线照射 HUVECs，并研究了从照射细胞短期孵育条件培养基中分离出的 ecDNA(R) 对完整 HUVECs 的影响。照射细胞产生的 ecDNA(R)对未照射 HUVECs 中 ROS 和 NO 产生的影响类似于旁观者效应。这些效应至少部分依赖于 TLR9 信号转导。我们比较了以下三种情况中人内皮细胞的一氧化氮和活性氧的产生：（1）低剂量照射；（2）暴露于从照射细胞的培养基中提取的 ecDNA(R)；（3）暴露于体外氧化的人 DNA。我们发现，对上述三种刺激物的细胞反应基本相似。我们得出结论，ecDNA 的辐射相关氧化是 ecDNA 介导的旁观者效应的重要组成部分。
