Quantitative analysis of isolated and clustered DNA damage induced by gamma-rays, carbon ion beams, and iron ion beams
Quantitative analysis of isolated and clustered DNA damage induced by gamma-rays, carbon ion beams, and iron ion beams
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DOI：
10.1269/jrr.07089
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发表时间：
2008-03-01
影响因子：
2
通讯作者：
Ide, Hiroshi
中科院分区：
文献类型：
--
作者：
Terato, Hiroaki;Tanaka, Ruri;Ide, Hiroshi
电离辐射在DNA中诱导多个损伤位点（簇状损伤）以及孤立的损伤。辐射损伤包括DNA几个螺旋圈内的密集损伤，被认为是理解电离辐射生物后果的关键。本研究采用γ射线、碳离子束和铁离子束分别辐照超螺旋质粒DNA和线性λ DNA，对单链DNA和双链成簇DNA损伤的光谱和产率进行了全面分析。尽管使用不同的方法进行损伤分析，质粒和λ DNA的实验给出了基本一致的结果。孤立和集群损伤的光谱基本上是独立的电离辐射用于照射的质量。聚束损伤和孤立损伤的产额随着不同辐射束的顺序γ> C > Fe而降低，因此表现出与LET [γ（0.2 keV/μ m）< C（13 keV/μ m）< Fe（200 keV/μ m）]的负相关性。与体外数据相一致，染色体DNA DSB的产量随着不同LET的碳离子束照射的中国仓鼠细胞中LET的增加而降低，这表明随着LET的增加，簇状损伤的产量降低并不是DNA体外照射所特有的，而是体外和体内照射所共有的。这些结果表明，电离辐射的不良生物效应不能简单地解释成簇的DNA损伤的产量，和的复杂性的成簇的损伤需要考虑到了解电离辐射的生物后果。
Ionizing radiation induces multiple damaged sites (clustered damage) together with isolated lesions in DNA. Clustered damage consists of closely spaced lesions within a few helical turns of DNA and is considered to be crucial for understanding the biological consequences of ionizing radiation. In the present study, two types of DNA, supercoiled plasmid DNA and linear lambda DNA, were irradiated with gamma-rays, carbon ion beams, and iron ion beams, and the spectra and yield of isolated DNA damage and bistranded clustered DNA damage were fully analyzed. Despite using different methods for damage analysis, the experiments with plasmid and lambda DNA gave largely consistent results. The spectra of both isolated and clustered damage were essentially independent of the quality of the ionizing radiation used for irradiation. The yields of clustered damage as well as of isolated damage decreased with the different radiation beams in the order gamma > C > Fe, thus exhibiting an inverse correlation with LET [gamma (0.2 keV/mu m) < C (13 keV/mu m) < Fe (200 keV/mu m)]. Consistent with in vitro data, the yield of chromosomal DNA DSBs decreased with increasing LET in Chinese hamster cells irradiated with carbon ion beams with different LETs, suggesting that the decrease in the yield of clustered damage with increasing LET is not peculiar to in vitro irradiation of DNA, but is common for both in vitro and in vivo irradiation. These results suggest that the adverse biological effect of the ionizing radiation is not simply accounted for by the yield of clustered DNA damage, and that the complexity of the clustered damage needs to be considered to understand the biological consequences of ionizing radiation.