a Stress biology Lab , UGC-DAE Consortium for Scientific Research, Kolkata Centre , Kolkata , West Bengal , India.
Int J Radiat Biol. 2019 Mar;95(3):243-263. doi: 10.1080/09553002.2019.1547440. Epub 2019 Jan 9.
Despite the extensive utilization of radiotherapy in cancer treatments, clinicians often face challenges in achieving desired outcomes. This is because of the existence of secondary radiation effects like bystander phenomenon that influence radiation nontargeted cells and tissues. The concept of bystander effects of radiation was first proposed in the latter half of the last century which led to a paradigm shift in classical dogma of radiation biology. This review primarily focuses on the diverse mechanisms of bystander signal production and response under the influence of different sources of radiation like α-, β-, γ rays as well as protons and ions. The dependency of bystander effects on cell type and linear energies are also reviewed. Furthermore, the reciprocal effects exerted by bystander cells on radiation-targeted cells have been discussed. Radiation-induced signaling in targeted cells stimulates the release of different mediators that induce a plethora of molecular effects on adjacent unirradiated cells, leading to cell death or proliferation. These responses are regulated by the cell type and linear energies of radiation. Different radiation sources have diverse damaging impacts on bystander cells wherein the complex interplay of signaling molecules, inflammation, apoptosis, necrosis, and autophagy determine the fate of the cells. Further, the feedback mechanism of bystander cells controls the severity of effects in radiation-targeted cells. From the existing literature, it is difficult to speculate how far the fundamental mechanisms of induction of bystander effects by irradiated cancer cells differ from that of normal cells, although cell-specific responses are observed in bystander cells. To have an accurate idea about the actual scenario, consideration of all possible variations of experimental conditions is necessary. This is crucial for optimal utilization of radiotherapy protocols to serve twofold purposes, increase radiotherapy efficiency while causing minimal health risks.
尽管放疗在癌症治疗中得到了广泛应用，但临床医生在实现预期治疗效果时常常面临挑战。这是因为存在着二次辐射效应，如旁观者效应，它会影响辐射非靶向细胞和组织。辐射旁观者效应的概念是在上世纪后半叶首次提出的，这导致了放射生物学经典教条的范式转变。这篇综述主要关注不同辐射源（如α、β、γ射线以及质子和离子）影响下旁观者信号产生和反应的多种机制。还综述了旁观者效应对细胞类型和线性能量的依赖性。此外，还讨论了旁观者细胞对辐射靶向细胞的反向效应。靶向细胞中的辐射诱导信号刺激不同介质的释放，这些介质会对未受辐射的相邻细胞产生大量分子效应，导致细胞死亡或增殖。这些反应受细胞类型和辐射线性能量的调节。不同的辐射源对旁观者细胞有不同的损伤影响，其中信号分子、炎症、细胞凋亡、细胞坏死和自噬的复杂相互作用决定了细胞的命运。此外，旁观者细胞的反馈机制控制了辐射靶向细胞中效应的严重程度。从现有文献中很难推断出受照射癌细胞诱导旁观者效应的基本机制与正常细胞有多大的不同，尽管旁观者细胞中观察到了细胞特异性反应。为了准确了解实际情况，有必要考虑实验条件的所有可能变化。这对于优化放疗方案的利用至关重要，既可以提高放疗效率，又可以将健康风险降至最低。
