Wright Eric G
University of Dundee, Department of Molecular and Cellular Pathology, Ninewells Hospital and Medical School, Dundee, Scotland, UK.
Hum Exp Toxicol. 2004 Feb;23(2):91-4. doi: 10.1191/0960327104ht424oa.
The paradigm of genetic alterations being restricted to direct DNA damage after exposure to ionizing radiation has been challenged by observations in which effects of ionizing radiation arise in cells that in themselves receive no radiation exposure. These effects are demonstrated in cells that are the descendants of irradiated cells (radiation-induced genomic instability) or in cells that are in contact with irradiated cells or receive certain signals from irradiated cells (radiation-induced bystander effects). Bystander signals may be transmitted either by direct intercellular communication through gap junctions, or by diffusible factors, such as cytokines released from irradiated cells. In both phenomena, the untargeted effects of ionizing radiation appear to be associated with free radical-mediated processes. There is evidence that radiation-induced genomic instability may be a consequence of, and in some cell systems may also produce, bystander interactions involving intercellular signalling, production of cytokines and free radical generation. These processes are also features of inflammatory responses that are known to have the potential for both bystander-mediated and persisting damage as well as for conferring a predisposition to malignancy. Thus, radiation-induced genomic instability and untargeted bystander effects may reflect interrelated aspects of inflammatory type responses to radiation-induced stress and injury and contribute to the variety of the pathological consequences of radiation exposures.
电离辐射暴露后基因改变仅限于直接DNA损伤的范式，已受到一些观察结果的挑战，即在自身未接受辐射暴露的细胞中也出现了电离辐射的效应。这些效应在受辐照细胞的后代细胞中得到证实（辐射诱导的基因组不稳定性），或在与受辐照细胞接触或从受辐照细胞接收某些信号的细胞中得到证实（辐射诱导的旁观者效应）。旁观者信号可能通过间隙连接进行直接细胞间通讯来传递，也可能通过可扩散因子来传递，例如从受辐照细胞释放的细胞因子。在这两种现象中，电离辐射的非靶向效应似乎都与自由基介导的过程有关。有证据表明，辐射诱导的基因组不稳定性可能是涉及细胞间信号传导、细胞因子产生和自由基生成的旁观者相互作用的结果，并且在某些细胞系统中也可能产生这种相互作用。这些过程也是炎症反应的特征，已知炎症反应既有旁观者介导的和持续的损伤的可能性，也有导致恶性肿瘤易感性的可能性。因此，辐射诱导的基因组不稳定性和非靶向旁观者效应可能反映了对辐射诱导的应激和损伤的炎症型反应的相互关联的方面，并促成了辐射暴露的各种病理后果。
