Low- and High-LET Ionizing Radiation Induces Delayed Homologous Recombination that Persists for Two Weeks before Resolving.
Low- and High-LET Ionizing Radiation Induces Delayed Homologous Recombination that Persists for Two Weeks before Resolving.
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DOI：
10.1667/rr14748.1
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发表时间：
2017-07
影响因子：
3.4
通讯作者：
Nickoloff JA
中科院分区：
文献类型：
--
作者：
Allen CP;Hirakawa H;Nakajima NI;Moore S;Nie J;Sharma N;Sugiura M;Hoki Y;Araki R;Abe M;Okayasu R;Fujimori A;Nickoloff JA
基因组不稳定是癌细胞的标志，DNA修复途径的失调或缺陷导致基因组不稳定，并与遗传性癌症易感性综合征有关。电离辐射可在照射后数小时或数天内引起突变或细胞死亡等直接影响。电离辐射在照射后也会引起许多代细胞的延迟效应。延迟效应包括高突变、超同源重组、染色体不稳定和克隆性存活减少（延迟死亡）。延迟性超重组（DHR）在机制上不同于延迟性染色体不稳定性和延迟性死亡。使用绿色荧光蛋白（GFP）直接重复同源重组系统，延时显微镜和基于菌落的分析，我们证明了DHR在低let X射线和高let碳离子辐射下增加了几倍。对DHR的延时分析显示，在基于菌落的分析中未检测到两类重组，包括重组后衰老或死亡的细胞。无论是低辐射传统还是高辐射传统，在放射后的前两周DHR都很明显，但在第三周消退到本底水平。结果表明，与低let辐射相比，高let辐射下的DHR介导的辐射诱导基因组不稳定的风险很少或没有额外的风险。
Genome instability is a hallmark of cancer cells and dysregulation or defects in DNA repair pathways cause genome instability and are linked to inherited cancer predisposition syndromes. Ionizing radiation can cause immediate effects such as mutation or cell death, observed within hours or a few days after irradiation. Ionizing radiation also induces delayed effects many cell generations after irradiation. Delayed effects include hypermutation, hyper-homologous recombination, chromosome instability and reduced clonogenic survival (delayed death). Delayed hyperrecombination (DHR) is mechanistically distinct from delayed chromosomal instability and delayed death. Using a green fluorescent protein (GFP) direct repeat homologous recombination system, time-lapse microscopy and colony-based assays, we demonstrate that DHR increases several-fold in response to low-LET X rays and high-LET carbon-ion radiation. Time-lapse analyses of DHR revealed two classes of recombinants not detected in colony-based assays, including cells that recombined and then senesced or died. With both low- and high-LETradiation, DHR was evident during the first two weeks postirradiation, but resolved to background levels during the third week. The results indicate that the risk of radiation-induced genome destabilization via DHR is time limited, and suggest that there is little or no additional risk of radiation-induced genome instability mediated by DHR with high-LET radiation compared to low-LET radiation.