The chemical stage of the Monte Carlo track-structure simulation code Geant4-DNA has been revised and validated. The root-mean-square (RMS) empirical parameter that dictates the displacement of water molecules after an ionization and excitation event in Geant4-DNA has been shortened to better fit experimental data. The pre-defined dissociation channels and branching ratios were not modified, but the reaction rate coefficients for simulating the chemical stage of water radiolysis were updated. The evaluation of Geant4-DNA was accomplished with TOPAS-nBio. For that, we compared predicted time-dependentGvalues in pure liquid water for·OH, e-aq, and H2with published experimental data. For H2O2and H·, simulation of added scavengers at different concentrations resulted in better agreement with measurements. In addition, DNA geometry information was integrated with chemistry simulation in TOPAS-nBio to realize reactions between radiolytic chemical species and DNA. This was used in the estimation of the yield of single-strand breaks (SSB) induced by137Csγ-ray radiolysis of supercoiled pUC18 plasmids dissolved in aerated solutions containing DMSO. The efficiency of SSB induction by reaction between radiolytic species and DNA used in the simulation was chosen to provide the best agreement with published measurements. An RMS displacement of 1.24 nm provided agreement with measured data within experimental uncertainties for time-dependentGvalues and under the presence of scavengers. SSB efficiencies of 24% and 0.5% for·OH and H·, respectively, led to an overall agreement of TOPAS-nBio results within experimental uncertainties. The efficiencies obtained agreed with values obtained with published non-homogeneous kinetic model and step-by-step Monte Carlo simulations but disagreed by 12% with published direct measurements. Improvement of the spatial resolution of the DNA damage model might mitigate such disagreement. In conclusion, with these improvements, Geant4-DNA/TOPAS-nBio provides a fast, accurate, and user-friendly tool for simulating DNA damage under low linear energy transfer irradiation.

Department of Basic Sciences School of Medicine Loma Linda University Loma Linda CA 92350 United States of America

Department of Radiation Dosimetry Nuclear Physics Institute of the Czech Academy of Sciences Prague Czech Republic

Department of Radiation Oncology Physics Division Massachusetts General Hospital and Harvard Medical School Boston MA United States of America

Department of Radiation Oncology Seoul National University Hospital Seoul 03080 Republic of Korea

Department of Radiation Oncology University of California San Francisco San Francisco CA 94115 United States of America

Facultad de Ciencias Físico Matemáticas Benemérita Universidad Autónoma de Puebla Puebla 72000 Mexico

Laboratoire de Dosimétrie des Rayonnements Ionisants Institut de Radioprotection et Sûreté Nucléaire Fontenay aux Roses BP 17 F 92262 France

Radiation Laboratory and Department of Physics University of Notre Dame Notre Dame IN 46556 United States of America

SLAC National Accelerator Laboratory Menlo Park CA United States of America

Univ Bordeaux CNRS CENBG UMR 5797 F 33170 Gradignan France

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