Quantification of DNA double‐strand breaks using Geant4‐DNA

Abstract

Purpose: This study aims to standardize the simulation procedure in measuring DNA double-strand breaks (DSBs), by using advanced Monte Carlo toolkits, and newly introduced experimental methods for DNA DSB measurement. Methods: For the experimental quantification of DNA DSB, an innovative DNA dosimeter was used to produce experimental data. GATE in combination with Geant4-DNA toolkit were exploited to simulate the experimental environment. The PDB4DNA example of Geant4-DNA was upgraded and investigated. Parameters of the simulation such energy threshold (ET) for a strand break and base pair threshold (BPT) for a DSB were evaluated, depending on the dose. Results: Simulations resulted to minimum differentiation in comparison to experimental data for ET = 19 AE 1 eV and BPT = 10 bp, and high differentiation for ET<17.5 eV or ET>22.5 eV and BPT = 10 bp. There was also small differentiation for ET = 17.5 eV and BPT = 6 bp. Uncertainty has been kept lower than 3%. Conclusions: This study includes first results on the quantification of DNA double-strand breaks. The energy spectrum of a LINAC was simulated and used for the first time to irradiate DNA molecules. Simulation outcome was validated on experimental data that were produced by a prototype DNA dosimeter.

Minibeam radiation therapy: A micro‐ and nano‐dosimetry Monte Carlo study

“…Thus, the quantification of DNA damage revealed by the clustering algorithm represented only potential clusters of SSBs or DSBs. To identify these clusters, three parameters were defined: The minimum number of energy transfer points composing a cluster was two. The maximal distance between two energy transfer points composing a cluster was 3.2 nm, as it is the distance between 10 base pairs, ensuring that the resulting clusters represented potential DSBs The minimal energy contained in a cluster was 10 eV or the minimal energy of each energy transfer point was 5 eV. …”

“…• The maximal distance between two energy transfer points composing a cluster was 3.2 nm, as it is the distance between 10 base pairs, ensuring that the resulting clusters represented potential DSBs. [39][40][41] • The minimal energy contained in a cluster was 10 eV or the minimal energy of each energy transfer point was 5 eV.…”

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

“…MCTS codes have been the workhorse of theoretical microdosimetry, enabling systematic calculations of lineal energy spectra (the stochastic analog of LET), proximity functions, ionization cluster distributions, etc., which are used for explaining and predicting the quality factor or the relative biological effectiveness of different ionizing radiations [33][34][35][36][37][38][39]. In addition, quantitative estimates of the early "direct" DNA damage can be obtained by combining the spatial distribution of energy-transfer points (above a certain threshold) with the geometric structure of DNA [40][41][42][43][44][45]. The main drawback of MCTS codes is that they are computer intensive and require much more detailed physics models than currently available ones [46].…”

“…Currently, there are two methods used to estimate DNA damage. The first method is to estimate potential DSBs by superimposing DNA geometry to the radiation track structure [42,44,[96][97][98]. The other method is to use clustering algorithms based on probabilistic models to estimate DSB yield [99][100][101].…”

“…Chatzipapas et al [42] quantified DNA DSBs that were produced when a DNA molecule was irradiated by a LINAC, using Geant4-DNA. They compared simulation results with experimental data that were produced in parallel with this work, using a prototype dosimeter described in this study [133].…”