Abstract
PurposeThis 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.MethodsFor 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.ResultsSimulations resulted to minimum differentiation in comparison to experimental data for ET = 19 ± 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%.ConclusionsThis 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.
Highlights
Because of the oxidative stress, every human cell experience more than 50,000 lesions that could lead to DNA mutations through reactive oxygen species (ROS),[1] produced by the aerobic metabolism
The purpose of this study was to investigate and standardize the Geant4-DNA simulation procedure for quantifying DNA-double-strand breaks (DSBs), we studied several cases with different combinations of energy and distance thresholds
The distance between two breaks that produce a DSB was set to 10 bp, which is the most frequently used value in the literature
Summary
Ionizing radiation can have both positive and negative influence on peoples’ health. It leads to genetic modifications that unless repaired, can lead to cell death. Because of the oxidative stress, every human cell experience more than 50,000 lesions that could lead to DNA mutations through reactive oxygen species (ROS),[1] produced by the aerobic metabolism. A dose of 2 Gy results to only ~3000 DNA lesions.[2]. DNA-doublestrand break (DSB) is reported in literature as a dominant factor for maleficent lesions produced by ionizing radiation, because even a single unrepaired one can cause cell death.[3–6]. DSB is called a break in the phosphodiester backbone of both DNA strands, separated by 10 base pairs (bp).[7–13]. The number of DSBs increases linearly with dose.[14] DNA-doublestrand break (DSB) is reported in literature as a dominant factor for maleficent lesions produced by ionizing radiation, because even a single unrepaired one can cause cell death.[3–6] DSB is called a break in the phosphodiester backbone of both DNA strands, separated by 10 base pairs (bp).[7–13] The number of DSBs increases linearly with dose.[14]
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