Spectrum of Radiation-Induced Clustered Non-DSB Damage - A Monte Carlo Track Structure Modeling and Calculations
Spectrum of Radiation-Induced Clustered Non-DSB Damage - A Monte Carlo Track Structure Modeling and Calculations
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DOI：
10.1667/rr13902.1
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发表时间：
2015-05-01
影响因子：
3.4
通讯作者：
Nikjoo, Hooshang
中科院分区：
文献类型：
--
作者：
Watanabe, Ritsuko;Rahmanian, Shirin;Nikjoo, Hooshang
本报告的目的是展示由计算机模拟产生的初始辐射诱导的细胞DNA损伤谱[特别关注非双链断裂（DSB）损伤]。本研究模拟的辐射类型为单能电子（100 eV-1.5 keV），超软x射线光子C k， Al k和Ti k，以及一些选定的离子，包括3.2 MeV/u的质子；0.74和2.4 MeV/u氦离子；氮离子29mev /u，铁离子950MeV/u。利用蒙特卡罗轨道结构方法模拟了这些类型的辐射在细胞模拟条件下由单轨道作用引起的损伤诱导。模拟考虑了直接能量沉积事件的作用和羟基自由基在包括水合水在内的几个螺旋旋转的原子线性B-DNA片段上的反应。我们的研究结果得出以下结论：a.不同类型损伤（碱基损伤，简单和复杂单链断裂（SSBs）和DSBs）的绝对水平因辐射类型而异；b.在各损伤类别中，简单损伤和复杂损伤的相对比例随辐射类型的不同而不同，高let辐射时，简单损伤和复杂损伤的相对比例较高；c.总体而言，无论是低let辐射还是高let辐射，碱基损伤对SSBs的产率之比相似，约为3.0 +/- 0.2；d.基极损伤对SSB和dsb复杂性的贡献大于额外的SSB损伤，这对低let辐射和高let辐射都是如此；e.低let辐射的平均SSB/DSB比值约为18，约为高let辐射的5倍。聚集性DNA损伤对细胞来说更难修复的假说在放射生物学家中广为流传。然而，到目前为止，还没有直接的体内实验方法来验证DNA修复动力学对DNA损伤复杂性的依赖性（包括DSB和非DSB类型）。本文提供的DNA损伤详细谱数据，特别是非dsb类型的DNA损伤，为检测碱基切除修复等DNA修复动力学机制模型提供了良好的基础。(C)辐射研究学会2015
The aim of this report is to present the spectrum of initial radiation-induced cellular DNA damage [with particular focus on non-double-strand break (DSB) damage] generated by computer simulations. The radiation types modeled in this study were monoenergetic electrons (100 eV-1.5 keV), ultrasoft X-ray photons C k, Al K and Ti K, as well as some selected ions including 3.2 MeV/u proton; 0.74 and 2.4 MeV/u helium ions; 29 MeV/u nitrogen ions and 950MeV/u iron ions. Monte Carlo track structure methods were used to simulate damage induction by these radiation types in a cell-mimetic condition from a single-track action. The simulations took into account the action of direct energy deposition events and the reaction of hydroxyl radicals on atomistic linear B-DNA segments of a few helical turns including the water of hydration. Our results permitted the following conclusions: a. The absolute levels of different types of damage [base damage, simple and complex single-strand breaks (SSBs) and DSBs] vary depending on the radiation type; b. Within each damage class, the relative proportions of simple and complex damage vary with radiation type, the latter being higher with high-LET radiations; c. Overall, for both low-and high-LET radiations, the ratios of the yields of base damage to SSBs are similar, being about 3.0 +/- 0.2; d. Base damage contributes more to the complexity of both SSBs and DSBs, than additional SSB damage and this is true for both low-and high-LET radiations; and e. The average SSB/DSB ratio for low-LET radiations is about 18, which is about 5 times higher than that for high-LET radiations. The hypothesis that clustered DNA damage is more difficult for cells to repair has gained currency among radiobiologists. However, as yet, there is no direct in vivo experimental method to validate the dependence of kinetics of DNA repair on DNA damage complexity (both DSB and non-DSB types). The data on the detailed spectrum of DNA damage presented here, in particular the non-DSB type, provide a good basis for testing mechanistic models of DNA repair kinetics such as base excision repair. (C) 2015 by Radiation Research Society