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

Matsuya, Yusuke; Nakano, Toshiaki*; Kai, Takeshi; Shikazono, Naoya*; Akamatsu, Ken*; Yoshii, Yuji*; Sato, Tatsuhiko

Among various DNA damage induced after irradiation, clustered damage composed of at least two vicinal lesions within from 10 to 20 base pairs is recognized as fatal damage to human tissue. Such clustered damage yields have been evaluated by means of computational approaches; however, the simulation validity has not been sufficiently made yet. Meanwhile, the experimental technique to detect clustered DNA damage has been evolved in the recent decades, so both approaches with simulation and experiment get used to be available for investigating clustered damage recently. In this study, we have developed a simple model for estimating clustered damage yield based on the spatial density of ionization and electronic excitation events obtained by the PHITS code, and compared the computational results to the experimental clustered damage coupled with base damage (BD) measured by gel electrophoresis and atomic force microscopy. The computational results agreed well with experimental fractions of clustered damage of strand breaks (SB) and BD, when the yield ratio of BD/SSB is assumed to be 1.3. From the comparison of complex DNA double-strand break coupled with BDs between simulation and experimental data, it was suggested that aggregation degree of the events along electron track reflects the complexity of DNA damage. The resent simulation enables to quantify the type of clustered damage which cannot be measured in in vitro experiment, which succeeded in interpreting the experimental detection efficiency for clustered BD.



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Category:Biochemistry & Molecular Biology



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