Prise Kevin M, Folkard Melvyn, Michael Barry D
Cell & Molecular Biophysics Group, Gray Cancer Institute, PO Box 100, Mount Vernon Hospital, Northwood, Middlesex, UK.
Oncogene. 2003 Oct 13;22(45):7043-9. doi: 10.1038/sj.onc.1206991.
Radiation-induced bystander responses are observed when cells respond to their neighbours being irradiated. Considerable evidence is now available regarding the importance of these responses in cell and tissue models. Most studies have utilized two approaches where either a media-transferable factor has been assessed or cells have been exposed to low fluences of charged particles, where only a few percent are exposed. The development of microbeams has allowed nontargeted responses such as bystander effects to be more carefully analysed. As well as charged particle microbeams, X-ray microprobes have been developed, and several groups are also developing electron microbeams. Using the Gray Cancer Institute soft X-ray microprobe, it has been possible to follow the response of individual cells to targeted low doses of carbon-characteristic soft X-rays. Studies in human fibroblasts have shown evidence of a significant radiation quality-dependent bystander effect, measured as chromosomal damage in the form of micronuclei which is radiation quality dependent. Other studies show that even under conditions when only a single cell is targeted with soft X-rays, significant bystander-mediated cell killing is observed. The observation of bystander responses with low LET radiation suggests that these may be important in understanding radiation risk from background levels of radiation, where cells observe only single electron track traversals. Also, the indirect evidence for these responses in vivo indicates that they may have a role to play in current radiotherapy approaches and future novel strategies involving modulating nontargeted responses.
当细胞对其邻近细胞受到辐射作出反应时，会观察到辐射诱导的旁观者效应。现在有大量证据表明这些效应在细胞和组织模型中的重要性。大多数研究采用了两种方法，一种是评估可通过介质传递的因子，另一种是让细胞暴露于低通量的带电粒子，其中只有百分之几的细胞受到照射。微束的发展使得旁观者效应等非靶向反应能够得到更仔细的分析。除了带电粒子微束，X射线微探针也已开发出来，还有几个研究小组也在开发电子微束。使用格雷癌症研究所的软X射线微探针，已经能够追踪单个细胞对靶向低剂量碳特征软X射线的反应。对人类成纤维细胞的研究表明，存在显著的辐射质量依赖性旁观者效应，以微核形式的染色体损伤来衡量，这种损伤取决于辐射质量。其他研究表明，即使在只有单个细胞受到软X射线靶向照射的条件下，也能观察到显著的旁观者介导的细胞杀伤。低传能线密度辐射旁观者效应的观察表明，这些效应对于理解背景辐射水平下的辐射风险可能很重要，因为在这种情况下细胞仅观察到单个电子径迹的穿行。此外，这些效应在体内的间接证据表明，它们可能在当前的放射治疗方法以及涉及调节非靶向反应的未来新策略中发挥作用。
