A Simplified Cluster Analysis of Electron Track Structure for Estimating Complex DNA Damage Yields
A Simplified Cluster Analysis of Electron Track Structure for Estimating Complex DNA Damage Yields
复制标题
DOI：
10.3390/ijms21051701
复制
发表时间：
2020-03-01
影响因子：
5.6
通讯作者：
Sato, Tatsuhiko
中科院分区：
文献类型：
--
作者：
Matsuya, Yusuke;Nakano, Toshiaki;Sato, Tatsuhiko
电离辐射引起的复杂DNA损伤是指在10-20个碱基对（bp）内至少有两个相邻的损伤，被认为是对人体组织的致命性损伤。由于在纳米尺度上直接测量DNA损伤的聚集性是困难的，许多基于Monte Carlo模拟的非弹性相互作用的聚类分析已经被用于评估DNA损伤。与此同时，检测复杂DNA损伤的实验技术在近几十年来不断发展，因此模拟和实验两种方法都被用于研究复杂DNA损伤。在这项研究中，我们提出了一个简化的聚类分析的电离和电子激发事件在10 bp内的轨道结构的基础上估计复杂的DNA损伤产率的电子和X射线照射。然后，我们比较计算结果与实验复杂的DNA损伤加上碱基损伤（BD）通过酶裂解和原子力显微镜（AFM）测量。计算结果与实验结果吻合较好，单链和双链断裂（SSB，DSB）和复杂的BD，当BD/SSB的产率比假定为1.3。考虑到复杂DSB产率的比较，即，DSB + BD和DSB + 2BD的模拟结果与实验结果比较，发现电子径迹沿着的事件聚集程度反映了诱导DNA损伤的复杂程度，其中43.5%的DSB可以归类为与BD耦合的复杂形式。本模拟使我们能够量化的复杂的损伤，不能通过在体外实验测量的类型，并帮助我们解释复杂的BD AFM测量的实验检测效率。这个简单的模型，用于估计复杂的DNA损伤产量有助于准确理解的DNA损伤的复杂性后，X射线和电子辐照。
Complex DNA damage, defined as at least two vicinal lesions within 10-20 base pairs (bp), induced after exposure to ionizing radiation, is recognized as fatal damage to human tissue. Due to the difficulty of directly measuring the aggregation of DNA damage at the nano-meter scale, many cluster analyses of inelastic interactions based on Monte Carlo simulation for radiation track structure in liquid water have been conducted to evaluate DNA damage. Meanwhile, the experimental technique to detect complex DNA damage has evolved in recent decades, so both approaches with simulation and experiment get used for investigating complex DNA damage. During this study, we propose a simplified cluster analysis of ionization and electronic excitation events within 10 bp based on track structure for estimating complex DNA damage yields for electron and X-ray irradiations. We then compare the computational results with the experimental complex DNA damage coupled with base damage (BD) measured by enzymatic cleavage and atomic force microscopy (AFM). The computational results agree well with experimental fractions of complex damage yields, i.e., single and double strand breaks (SSBs, DSBs) and complex BD, when the yield ratio of BD/SSB is assumed to be 1.3. Considering the comparison of complex DSB yields, i.e., DSB + BD and DSB + 2BD, between simulation and experimental data, we find that the aggregation degree of the events along electron tracks reflects the complexity of induced DNA damage, showing 43.5% of DSB induced after 70 kVp X-ray irradiation can be classified as a complex form coupled with BD. The present simulation enables us to quantify the type of complex damage which cannot be measured through in vitro experiments and helps us to interpret the experimental detection efficiency for complex BD measured by AFM. This simple model for estimating complex DNA damage yields contributes to the precise understanding of the DNA damage complexity induced after X-ray and electron irradiations.