Liu Cuihua, Hirakawa Hirokazu, Tanaka Kaoru, Mohd Saaya Fazliana, Nenoi Mitsuru, Fujimori Akira, Wang Bing
National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.
Medical Technology Division, Malaysian Nuclear Agency, Selangor, Malaysia.
Dose Response. 2019 Mar 4;17(1):1559325819833840. doi: 10.1177/1559325819833840. eCollection 2019 Jan-Mar.
Radiotherapy (RT) treats cancer effectively with high doses of ionizing radiation (IR) to killing cancer cells and shrinking tumors while bearing the risk of developing different side effects, including secondary cancer, which is most concerning for long-term health consequences. Genomic instability (GI) is a characteristic of most cancer cells, and IR-induced GI can manifest as delayed homologous recombination (HR). Radioadaptive response (RAR) is capable of reducing genotoxicity, cell transformation, mutation, and carcinogenesis, but the rational evidence describing its contributions to the reduction of radiation risk, in particular, carcinogenesis, remains fragmented. In this work, to investigate the impact of RAR on high-dose, IR-induced GI measured as delayed HR, the frequency of recombinant cells was comparatively studied under RAR-inducible and -uninducible conditions in the nucleated cells in hematopoietic tissues (bone marrow and spleen) using the Direct Repeat-green fluorescent protein (RaDR-GFP) homozygote mice. Results demonstrated that the frequency of recombinant cells was significantly lower in hematopoietic tissues under RAR-inducible condition. These findings suggest that reduction in delayed HR may be at least a part of the mechanisms underlying decreased carcinogenesis by RAR, and application of RAR would contribute to a more rigorous and scientifically grounded system of radiation protection in RT.
放射疗法（RT）通过高剂量电离辐射（IR）有效治疗癌症，以杀死癌细胞并缩小肿瘤，同时承担出现不同副作用的风险，包括继发性癌症，这对长期健康后果最为令人担忧。基因组不稳定性（GI）是大多数癌细胞的一个特征，IR诱导的GI可表现为延迟同源重组（HR）。放射适应性反应（RAR）能够降低遗传毒性、细胞转化、突变和致癌作用，但描述其对降低辐射风险（特别是致癌作用）贡献的合理证据仍然零散。在这项工作中，为了研究RAR对以延迟HR衡量的高剂量IR诱导的GI的影响，使用直接重复绿色荧光蛋白（RaDR-GFP）纯合子小鼠，在造血组织（骨髓和脾脏）有核细胞的RAR可诱导和不可诱导条件下，比较研究了重组细胞的频率。结果表明，在RAR可诱导条件下，造血组织中重组细胞的频率显著降低。这些发现表明，延迟HR的降低可能至少是RAR降低致癌作用潜在机制的一部分，RAR的应用将有助于建立一个更严格、更有科学依据的放射治疗辐射防护系统。
