University of Dundee, Centre for Oncology and Molecular Medicine, Division of Medical Sciences, Ninewells Hospital and Medical School, Dundee DD1 9SY, Scotland, UK.
Mutat Res. 2010 May 1;687(1-2):28-33. doi: 10.1016/j.mrfmmm.2010.01.014. Epub 2010 Jan 18.
A well-established radiobiological paradigm is that the biological effects of ionizing radiation occur in irradiated cells as a consequence of the DNA damage they incur. However, many observations of, so-called, non-targeted effects indicate that genetic alterations are not restricted to directly irradiated cells. Non-targeted effects are responses exhibited by non-irradiated cells that are the descendants of irradiated cells (radiation-induced genomic instability) or by cells that have communicated with irradiated cells (radiation-induced bystander effects). Radiation-induced genomic instability is characterized by chromosomal abnormalities, gene mutations and cell death. Similar effects, as well as responses that may be regarded as protective, have been attributed to bystander mechanisms. The majority of studies to date have used in vitro systems but some non-targeted effects have been demonstrated in vivo and there is also evidence for radiation-induced instability in the mammalian germ line. However, there may be situations where radiation-induced genomic instability in vivo may not necessarily identify genomically unstable somatic cells but the manifestation of responses to ongoing production of damaging signals generated by genotype-dependent mechanisms having properties in common with inflammatory processes. Non-targeted mechanisms have significant implications for understanding mechanisms of radiation action but the current state of knowledge does not permit definitive statements about whether these phenomena have implications for assessing radiation risk.
一个成熟的放射生物学范式是，电离辐射对细胞的生物学效应是由于它们造成的 DNA 损伤而发生的。然而，许多所谓的非靶向效应的观察表明，遗传改变不仅限于直接受照射的细胞。非靶向效应是指受照射细胞的后代（辐射诱导的基因组不稳定性）或与受照射细胞有过交流的细胞（辐射诱导的旁观者效应）表现出的反应。辐射诱导的基因组不稳定性的特征是染色体异常、基因突变和细胞死亡。类似的效应，以及可能被视为保护的反应，都归因于旁观者机制。迄今为止，大多数研究都使用了体外系统，但一些非靶向效应已在体内得到证实，哺乳动物生殖细胞中也有辐射诱导不稳定性的证据。然而，在某些情况下，体内辐射诱导的基因组不稳定性可能不一定能识别基因组不稳定的体细胞，而是对由与炎症过程具有共同特性的依赖于基因型的机制产生的持续损伤信号的反应的表现。非靶向机制对于理解辐射作用机制具有重要意义，但目前的知识状况还不能明确这些现象是否对评估辐射风险有影响。
