PURPOSE: The simulation of individual particle tracks and the chemical stage following water radiolysis in biological tissue is an effective means of improving our knowledge of the physico-chemical contribution to the biological effect of ionizing radiation. However, the step-by-step simulation of the reaction kinetics of radiolytic species is the most time-consuming task in Monte Carlo track-structure simulations, with long simulation times that are an impediment to research. In this work, we present the implementation of the independent reaction times (IRT) method in Geant4-DNA Monte Carlo toolkit to improve the computational efficiency of calculating G-values, defined as the number of chemical species created or lost per 100 eV of deposited energy. METHODS: The computational efficiency of IRT, as implemented, is compared to that from available Geant4-DNA step-by-step simulations for electrons, protons and alpha particles covering a wide range of linear energy transfer (LET). The accuracy of both methods is verified using published measured data from fast electron irradiations for • OH and e aq - for time-dependent G-values. For IRT, simulations in the presence of scavengers irradiated by cobalt-60 γ-ray and 2 MeV protons are compared with measured data for different scavenging capacities. In addition, a qualitative assessment comparing measured LET-dependent G-values with Geant4-DNA calculations in pure liquid water is presented. RESULTS: The IRT improved the computational efficiency by three orders of magnitude relative to the step-by-step method while differences in G-values by 3.9% at 1 μs were found. At 7 ps, • OH and e aq - yields calculated with IRT differed from recent published measured data by 5% ± 4% and 2% ± 4%, respectively. At 1 μs, differences were 9% ± 5% and 6% ± 7% for • OH and e aq - , respectively. Uncertainties are one standard deviation. Finally, G-values at different scavenging capacities and LET-dependent G-values reproduced the behavior of measurements for all radiation qualities. CONCLUSION: The comprehensive validation of the Geant4-DNA capabilities to accurately simulate the chemistry following water radiolysis is an ongoing work. The implementation presented in this work is a necessary step to facilitate performing such a task.

Centre d'Études Nucléaires de Bordeaux Gradignan Université de Bordeaux CNRS IN2P3 UMR5797 Gradignan 33175 France

Department of Radiation Convergence Engineering Yonsei University Wonju 26493 Korea

Department of Radiation Dosimetry Nuclear Physics Institute of the CAS Prague Czech Republic

Department of Radiation Oncology University of California San Francisco San Francisco CA 94115 USA

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

Institut de Radioprotection et de Sûreté Nucléaire IRSN BP17 Fontenay aux Roses 92262 France

KEK 1 1 Oho Tsukuba Ibaraki 305 0801 Japan

Radiation Laboratory University of Notre Dame Notre Dame IN 46556 USA

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Radium deposition in human brain tissue: A Geant4-DNA Monte Carlo toolkit study

DNA damage modeled with Geant4-DNA: effects of plasmid DNA conformation and experimental conditions

TOPAS-nBio validation for simulating water radiolysis and DNA damage under low-LET irradiation

Assessment of DNA damage with an adapted independent reaction time approach implemented in Geant4-DNA for the simulation of diffusion-controlled reactions between radio-induced reactive species and a chromatin fiber