Biosystems Group, Institute of Automatic Control, Faculty of Automatics, Electronics, and Informatics, Silesian University of Technology, 44-100 Gliwice, Poland.
Biosystems Group, Institute of Automatic Control, Faculty of Automatics, Electronics, and Informatics, Silesian University of Technology, 44-100 Gliwice, Poland.
Free Radic Biol Med. 2014 Mar;68:278-87. doi: 10.1016/j.freeradbiomed.2013.12.021. Epub 2013 Dec 27.
Radiation-induced bystander effects are various types of responses displayed by nonirradiated cells induced by signals transmitted from neighboring irradiated cells. This phenomenon has been well studied after ionizing radiation, but data on bystander effects after UV radiation are limited and so far have been reported mainly after UVA and UVB radiation. The studies described here were aimed at comparing the responses of human dermal fibroblasts exposed directly to UV (A, B, or C wavelength range) and searching for bystander effects induced in unexposed cells using a transwell co-incubation system. Cell survival and apoptosis were used as a measure of radiation effects. Additionally, induction of senescence in UV-exposed and bystander cells was evaluated. Reactive oxygen species (ROS), superoxide radical anions, and nitric oxide inside the cells and secretion of interleukins 6 and 8 (IL-6 and IL-8) into the medium were assayed and evaluated as potential mediators of bystander effects. All three regions of ultraviolet radiation induced bystander effects in unexposed cells, as shown by a diminution of survival and an increase in apoptosis, but the pattern of response to direct exposure and the bystander effects differed depending on the UV spectrum. Although UVA and UVB were more effective than UVC in generation of apoptosis in bystander cells, UVC induced senescence both in irradiated cells and in neighbors. The level of cellular ROS increased significantly shortly after UVA and UVB exposure, suggesting that the bystander effects may be mediated by ROS generated in cells by UV radiation. Interestingly, UVC was more effective at generation of ROS in bystanders than in directly exposed cells and induced a high yield of superoxide in exposed and bystander cells, which, however, was only weakly associated with impairment of mitochondrial membrane potential. Increasing concentration of IL-6 but not IL-8 after exposure to each of the three bands of UV points to its role as a mediator in the bystander effect. Nitric oxide appeared to play a minor role as a mediator of bystander effects in our experiments. The results demonstrating an increase in intracellular oxidation, not only in directly UV-exposed but also in neighboring cells, and generation of proinflammatory cytokines, processes entailing cell damage (decreased viability, apoptosis, senescence), suggest that all bands of UV radiation carry a potential hazard for human health, not only due to direct mechanisms, but also due to bystander effects.
辐射诱导的旁观者效应是指非照射细胞通过接受来自照射细胞的信号而表现出的各种类型的反应。这种现象在电离辐射后已经得到了很好的研究，但关于紫外线辐射后旁观者效应的数据有限，迄今为止，主要报道的是 UVA 和 UVB 辐射后的旁观者效应。这里描述的研究旨在比较直接暴露于紫外线（A、B 或 C 波长范围）的人真皮成纤维细胞的反应，并使用 Transwell 共孵育系统寻找未暴露细胞中的旁观者效应。细胞存活和凋亡被用作辐射效应的测量指标。此外，还评估了紫外线照射和旁观者细胞中的衰老诱导。细胞内活性氧（ROS）、超氧阴离子自由基和一氧化氮的产生以及细胞因子白细胞介素 6 和 8（IL-6 和 IL-8）分泌到培养基中被测定和评估为旁观者效应的潜在介质。所有三种紫外线区域都诱导了未暴露细胞中的旁观者效应，表现为存活减少和凋亡增加，但对直接暴露和旁观者效应的反应模式因 UV 光谱而异。尽管 UVA 和 UVB 比 UVC 更有效地诱导旁观者细胞凋亡，但 UVC 诱导了照射细胞和邻居细胞的衰老。UVA 和 UVB 暴露后不久，细胞内 ROS 水平显著增加，表明旁观者效应可能是由紫外线辐射在细胞中产生的 ROS 介导的。有趣的是，UVC 在旁观者细胞中产生 ROS 的效率高于直接暴露的细胞，并且在暴露的和旁观者的细胞中诱导了高产量的超氧自由基，然而，这与线粒体膜电位的损伤仅弱相关。暴露于三种紫外线波段后，IL-6 而不是 IL-8 的浓度增加表明其在旁观者效应中作为介质的作用。在我们的实验中，一氧化氮似乎作为旁观者效应的介质作用较小。实验结果表明，不仅在直接紫外线照射的细胞中，而且在相邻细胞中，细胞内氧化增加，以及促炎细胞因子的产生，这些过程都涉及细胞损伤（细胞活力降低、凋亡、衰老），这表明所有紫外线波段都对人类健康构成潜在危害，不仅由于直接机制，还由于旁观者效应。
