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Open AccessArticle

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

1
Nuclear Science and Engineering Center, Research Group for Radiation Transport Analysis, Japan Atomic Energy Agency, 2-4 Shirakata, Tokai, Ibaraki 319-1195, Japan
2
Department of Quantum life Science, Quantum Beam Science Research Directorate, National Institutes of Quantum and Radiological Science and Technology, 8-1-7 Umemidai, Kizugawa-shi, Kyoto 619-0215, Japan
3
Central Institute of Isotope Science, Hokkaido University, Kita-15 Nishi-7, Kita-ku, Sapporo, Hokkaido 060-0815, Japan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(5), 1701; https://doi.org/10.3390/ijms21051701
Received: 30 January 2020 / Revised: 27 February 2020 / Accepted: 28 February 2020 / Published: 2 March 2020
(This article belongs to the Special Issue Radiation Damage in Biomolecules and Cells)
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. View Full-Text
Keywords: Monte Carlo radiation transport; complex DNA damage coupled with base damage; modelling of DNA damage yields Monte Carlo radiation transport; complex DNA damage coupled with base damage; modelling of DNA damage yields
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Matsuya, Y.; Nakano, T.; Kai, T.; Shikazono, N.; Akamatsu, K.; Yoshii, Y.; Sato, T. A Simplified Cluster Analysis of Electron Track Structure for Estimating Complex DNA Damage Yields. Int. J. Mol. Sci. 2020, 21, 1701.

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