Penninckx Sébastien, Pariset Eloise, Cekanaviciute Egle, Costes Sylvain V
Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
Space Biosciences Division, NASA Ames Research Center, Moffett Field, CA 94035, USA.
NAR Cancer. 2021 Dec 22;3(4):zcab046. doi: 10.1093/narcan/zcab046. eCollection 2021 Dec.
Radiation-induced foci (RIF) are nuclear puncta visualized by immunostaining of proteins that regulate DNA double-strand break (DSB) repair after exposure to ionizing radiation. RIF are a standard metric for measuring DSB formation and repair in clinical, environmental and space radiobiology. The time course and dose dependence of their formation has great potential to predict responses to ionizing radiation, predisposition to cancer and probability of adverse reactions to radiotherapy. However, increasing complexity of experimentally and therapeutically setups (charged particle, FLASH …) is associated with several confounding factors that must be taken into account when interpreting RIF values. In this review, we discuss the spatiotemporal characteristics of RIF development after irradiation, addressing the common confounding factors, including cell proliferation and foci merging. We also describe the relevant endpoints and mathematical models that enable accurate biological interpretation of RIF formation and resolution. Finally, we discuss the use of RIF as a biomarker for quantification and prediction of radiation responses, including important caveats relating to the choice of the biological endpoint and the detection method. This review intends to help scientific community design radiobiology experiments using RIF as a key metric and to provide suggestions for their biological interpretation.
辐射诱导灶（RIF）是通过对暴露于电离辐射后调节DNA双链断裂（DSB）修复的蛋白质进行免疫染色而可视化的核斑点。RIF是临床、环境和空间放射生物学中测量DSB形成和修复的标准指标。其形成的时间进程和剂量依赖性在预测对电离辐射的反应、患癌易感性以及放疗不良反应概率方面具有巨大潜力。然而，实验和治疗设置（带电粒子、FLASH……）的日益复杂性与几个混杂因素相关，在解释RIF值时必须考虑这些因素。在本综述中，我们讨论了辐照后RIF发展的时空特征，阐述了常见的混杂因素，包括细胞增殖和病灶合并。我们还描述了相关的终点指标和数学模型，这些能够对RIF的形成和消退进行准确的生物学解释。最后，我们讨论了将RIF用作辐射反应定量和预测生物标志物的情况，包括与生物学终点选择和检测方法相关的重要注意事项。本综述旨在帮助科学界设计以RIF作为关键指标的放射生物学实验，并为其实验结果的生物学解释提供建议。
