Habash Mohammad, Bohorquez Luis C, Kyriakou Elizabeth, Kron Tomas, Martin Olga A, Blyth Benjamin J
Cancer Research Division, Peter MacCallum Cancer Centre, 305 Grattan Street, Parkville, VIC 3000, Australia.
Faculty of Medicine, Dentistry & Health Sciences, The University of Melbourne, Parkville, VIC 3010, Australia.
Cancers (Basel). 2017 Oct 27;9(11):147. doi: 10.3390/cancers9110147.
Whilst the near instantaneous physical interaction of radiation energy with living cells leaves little opportunity for inter-individual variation in the initial yield of DNA damage, all the downstream processes in how damage is recognized, repaired or resolved and therefore the ultimate fate of cells can vary across the population. In the clinic, this variability is observed most readily as rare extreme sensitivity to radiotherapy with acute and late tissue toxic reactions. Though some radiosensitivity can be anticipated in individuals with known genetic predispositions manifest through recognizable phenotypes and clinical presentations, others exhibit unexpected radiosensitivity which nevertheless has an underlying genetic cause. Currently, functional assays for cellular radiosensitivity represent a strategy to identify patients with potential radiosensitivity before radiotherapy begins, without needing to discover or evaluate the impact of the precise genetic determinants. Yet, some of the genes responsible for extreme radiosensitivity would also be expected to confer susceptibility to radiation-induced cancer, which can be considered another late adverse event associated with radiotherapy. Here, the utility of functional assays of radiosensitivity for identifying individuals susceptible to radiotherapy-induced second cancer is discussed, considering both the common mechanisms and important differences between stochastic radiation carcinogenesis and the range of deterministic acute and late toxic effects of radiotherapy.
虽然辐射能量与活细胞的近乎即时的物理相互作用使得DNA损伤的初始产率几乎没有个体间差异的机会，但在损伤如何被识别、修复或解决以及细胞的最终命运等所有下游过程在人群中可能会有所不同。在临床上，这种变异性最容易表现为对放疗的罕见极端敏感性，并伴有急性和晚期组织毒性反应。虽然对于那些通过可识别的表型和临床表现表现出已知遗传易感性的个体，可以预期其有一定的放射敏感性，但其他个体则表现出意想不到的放射敏感性，不过其背后有遗传原因。目前，细胞放射敏感性的功能测定是一种在放疗开始前识别潜在放射敏感性患者的策略，而无需发现或评估精确遗传决定因素的影响。然而，一些导致极端放射敏感性的基因也可能会使人易患辐射诱发的癌症，这可被视为与放疗相关的另一种晚期不良事件。在此，讨论了放射敏感性功能测定在识别易患放疗诱发的第二种癌症个体方面的实用性，同时考虑了随机辐射致癌作用与放疗的一系列确定性急性和晚期毒性效应之间的共同机制和重要差异。
