A Simplified Cluster Analysis of Electron Track Structure for Estimating Complex DNA Damage Yields

作者：Yusuke Matsuya, Toshiaki Nakano, Takeshi Kai, Naoya Shikazono, Ken Akamatsu, Yuji Yoshii, Tatsuhiko Sato · 发表于：International Journal of Molecular Sciences · 年份：2020 · DOI：10.3390/ijms21051701 · 被引用次数：25 · 研究领域：Electron and X-Ray Spectroscopy Techniques、Radiation Therapy and Dosimetry、DNA Repair Mechanisms

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,...