Bystander effects induced by diffusing mediators after photodynamic stress.
Bystander effects induced by diffusing mediators after photodynamic stress.
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DOI：
10.1667/rr1669.1
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发表时间：
2009-07
影响因子：
3.4
通讯作者：
Redmond RW
中科院分区：
文献类型：
--
作者：
Chakraborty A;Held KD;Prise KM;Liber HL;Redmond RW
旁观者效应，即细胞不被电离辐射穿过时，在接近照射的细胞表现出各种反应，是有据可查的辐射生物学领域，在这里，我们表明，相当多的旁观者反应后，也观察到光动力应力使用膜定位染料次卟啉（DP）。使用悬浮液中的WTK 1人淋巴母细胞样细胞系的细胞和排除靶细胞和旁观者细胞之间接触的transwell插入系统，我们已经证明了旁观者信号传导是由扩散物质介导的。所用光敏剂的核内定位表明，原发性DNA损伤不是引发这些旁观者反应的触发因素，这些旁观者反应包括氧化应激升高、DNA损伤（微核形成）、诱变和克隆形成存活率降低。此外，在旁观者人群中的氧化应激减少了膜抗氧化剂维生素E在靶细胞的存在下，这表明脂质过氧化可能在介导这些旁观者效应中发挥关键作用。这些旁观者效应的注量响应是非线性的，在较低的注量和对靶细胞群体的毒性下观察到较大的效应。因此，当考虑光动力作用在细胞和组织中的结果时，旁观者效应可能是显著的，特别是在亚致死剂量下。
The bystander effect, whereby cells that are not traversed by ionizing radiation exhibit various responses when in proximity to irradiated cells, is well documented in the field of radiation biology, Here we demonstrate that considerable bystander responses are also observed after photodynamic stress using the membrane-localizing dye deuteroporphyrin (DP). Using cells of a WTK1 human lymphoblastoid cell line in suspension and a transwell insert system that precludes contact between targeted and bystander cells, we have shown that the bystander signaling is mediated by diffusing species. The extranuclear localization of the photosensitizer used suggests that primary DNA damage is not the trigger for initiating these bystander responses, which include elevated oxidative stress, DNA damage (micronucleus formation), mutagenesis and decreased clonogenic survival. In addition, oxidative stress in the bystander population was reduced by the presence of the membrane antioxidant vitamin E in the targeted cells, suggesting that lipid peroxidation may play a key role in mediating these bystander effects. The fluence responses for these bystander effects are non-linear, with larger effects seen at lower fluences and toxicity to the target cell population. Hence, when considering outcomes of photodynamic action in cells and tissue, bystander effects may be significant, especially at sublethal fluences.