Modeling of yield estimation for DNA strand breaks based on Monte Carlo simulations of electron track structure in liquid water

Abstract

DNA strand breaks are induced in cells mainly composed of liquid water along ionizing radiation tracks. For estimating DNA strand break yields, track structures for electrons in liquid water in Monte Carlo simulations are of great importance; however, detailed simulations to obtain both energy deposition and free radical reaction to DNA are time-consuming processes. Here, we present a simple model for estimating yields of single-and double-strand breaks (SSB, DSB, and DSB/SSB ratio) based only on spatial patterns of inelastic interactions (i.e., ionization and electronic excitation) generated by electrons, which are evaluated by the track structure mode of Particle and Heavy Ion Transport code System without analyzing the production and diffusion of free radicals. In the present model, the number of events per track and that of a pair composed of two events within 3.4 nm (10 base pairs) were stochastically sampled for calculating SSB and DSB yields. The results calculated by this model agree well with other simulations and experimental data on the DSB yield and the DSB/SSB ratio for monoenergetic electron irradiation. This model also demonstrates the relative biological effectiveness at the DSB endpoint for various photon irradiations, indicating that the spatial pattern composed of ionization and electronic excitation without physicochemical and chemical stages is sufficient to obtain the impact of electrons on the initial DNA strand break induction.

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

“…We also show Y DSB and Y DSB /Y SSB using the blue square in Figure 3 to compare Y DSB with Y cBD . As reported previously [17], the peak of the number of linkages per incident electron energy was found to be around 0.3 keV electrons. The maximum Y DSB and Y cBD for a 10 bp cluster size (L c = 10 bp) also were found to be 3.24 × 10 −11 (Gy −1 Da −1 ) (Y DSB /Y SSB = 14.5%) and 4.58 × 10 −11 (Gy −1 Da −1 ) (Y cBD /Y BD = 16.2%), respectively.…”

“…The present model with the PHITS calculation indicates that more than 20-30% of DSBs can be classified as complex forms. Among the 0.3 keV, 1 keV, 10 keV and 100 keV electrons, the yield of DSBs in the case of the 0.3 keV electron is highest [17], while the fraction of complex DSBs (cDSBs composed of DSB+ and DSB++) for the case of 1 keV electron is highest. This comparison indicates that the present model can reproduce the simulation results by using a different prediction model from the previous simulations [44,45], suggesting that this identification approach for complex damage type using the number of events in sites with a 10 bp radius (9 and 12 events for inducing a BD and a SB at each DSB site, respectively) is reasonable.…”

“…Among various 2 of 13 DNA damage types [8,9], DNA double-strand breaks (DSBs), defined as two strand breaks within 10 base pairs (bp) [2,10,11] are conventionally recognized as fatal DNA damage, which can lead to cell death with a certain probability [12]. Therefore, the relative biological effectiveness (RBE) at the endpoints of DSBs and cell survival has been investigated in vitro and in silico in previous reports [2,6,8,9,[12][13][14][15][16][17][18][19]. Additionally, complex DNA damage composed of at least three vicinal lesions caused within 10-20 bp, such as DSBs coupled with strand breaks or base damage (BD), is believed to be more lethal to cells than simple DSBs [20,21] due to refractory damage [22,23].…”

“…A cluster analysis of inelastic interactions based on a radiation track structure in liquid water has been conducted as a powerful tool for estimating DNA damage yield [2,3,8,16,42]. The aim of this study is to develop a simple model for estimating complex DNA damage (i.e., isolated DSB, DSB + BD, DSB + 2BD, 2BD, 3BD, 4BD) based on previous simulation techniques [17,27,28], and to investigate the simulation accuracy and the nature of X-ray-(and electron-) induced complex damage in comparison with experimental data. This work finally quantifies the complexity of DNA damage under X-ray and electron irradiations.…”

Ionizing Radiation and Complex DNA Damage: Quantifying the Radiobiological Damage Using Monte Carlo Simulations

“…MC4 performs simulations down to very low energies, including models for gaseous and liquid water, and is known for its upgraded models for the liquid phase [68,69]. PHITS has been developed to simulate the track structure of electrons in liquid water in a wide incident energy spectrum from 1 meV to 1 MeV [70].…”