Kadhim M A, Hill M A
Genomic Instability Group, Department of Biological and Medical Sciences, Oxford Brookes University, Gipsy Lane, Oxford OX3 0BP, UK
CRUK/MRC Gray Institute for Radiation Oncology and Biology, University of Oxford, ORCRB Roosevelt Drive, Oxford OX3 7DQ, UK.
Radiat Prot Dosimetry. 2015 Sep;166(1-4):118-24. doi: 10.1093/rpd/ncv167. Epub 2015 Apr 20.
The target theory of radiation-induced effects has been challenged by numerous studies, which indicate that in addition to biological effects resulting from direct DNA damage within the cell, a variety of non-DNA targeted effects (NTE) may make important contributions to the overall outcome. Ionising radiation induces complex, global cellular responses, such as genomic instability (GI) in both irradiated and never-irradiated 'bystander' cells that receive molecular signals produced by irradiated cells. GI is a well-known feature of many cancers, increasing the probability of cells to acquire the 'hallmarks of cancer' during the development of tumours. Although epidemiological data include contributions of both direct and NTE, they lack (i) statistical power at low dose where differences in dose response for NTE and direct effects are likely to be more important and (ii) heterogeneity of non-targeted responses due to genetic variability between individuals. In this article, NTE focussing on GI and bystander effects were critically examined, the specific principles of NTE were discussed and the potential influence on human health risk assessment from low-dose radiation was considered.
辐射诱导效应的靶理论受到了众多研究的挑战，这些研究表明，除了细胞内直接DNA损伤产生的生物学效应外，多种非DNA靶向效应（NTE）可能对总体结果有重要贡献。电离辐射会引发复杂的、全身性的细胞反应，例如在受照射细胞和从未受照射但接收受照射细胞产生的分子信号的“旁观者”细胞中都会出现基因组不稳定（GI）。GI是许多癌症的一个众所周知的特征，在肿瘤发展过程中会增加细胞获得“癌症特征”的可能性。尽管流行病学数据包含直接效应和NTE的影响，但它们缺乏（i）在低剂量下的统计效力，而在低剂量时NTE和直接效应的剂量反应差异可能更为重要，以及（ii）由于个体间遗传变异性导致的非靶向反应的异质性。在本文中，对聚焦于GI和旁观者效应的NTE进行了批判性审视，讨论了NTE的具体原理，并考虑了其对低剂量辐射人类健康风险评估的潜在影响。
