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.

Hoang Ngoc Tran,Václav Štěpán,Mathieu Karamitros,Wook‐Geun Shin,Marie Davídková,José Ramos‐Méndez,Bruce Faddegon,Yann Perrot,Shogo Okada,Sébastien Incerti,Carmen Villagrasa

doi:10.1002/mp.14612

Abstract

PurposeSimulation of indirect damage originating from the attack of free radical species produced by ionizing radiation on biological molecules based on the independent pair approximation is investigated in this work. In addition, a new approach, relying on the independent pair approximation that is at the origin of the independent reaction time (IRT) method, is proposed in the chemical stage of Geant4‐DNA.MethodsThis new approach has been designed to respect the current Geant4‐DNA chemistry framework while proposing a variant IRT method. Based on the synchronous algorithm, this implementation allows us to access the information concerning the position of radicals and may make it more convenient for biological damage simulations. Estimates of the evolution of free species as well as biological hits in a segment of DNA chromatin fiber in Geant4‐DNA were compared for the dynamic time step approach of the step‐by‐step (SBS) method, currently used in Geant4‐DNA, and this newly implemented IRT.ResultsResults show a gain in computation time of a factor of 30 for high LET particle tracks with a better than 10% agreement on the number of DNA hits between the value obtained with the IRT method as implemented in this work and the SBS method currently available in Geant4‐DNA.ConclusionOffering in Geant4‐DNA more efficient methods for the chemical step based on the IRT method is a task in progress. For the calculation of biological damage, information on the position of chemical species is a crucial point. This can be achieved using the method presented in this paper.

Highlights

Among the possible causes of the effects induced by ionizing radiation on living organisms, DNA damage is of particular interest[1] and many techniques are being developed to both measure and predict it
The reliability and performance of our independent time reaction (IRT) method implementation in Geant4-DNA are examined by using this method in the simulation to calculate time-dependent G-values of the chemical species created by water radiolysis, and comparing the results with other simulated data and experimental data from the literature
These quantities were calculated with our IRT method implementation, the SBS-dynamic time step of the current public release of Geant4-DNA (Geant4 10.6), and the IRT method of TOPAS-nBio code (Topas-IRT).[23]

Summary

Introduction

Among the possible causes of the effects induced by ionizing radiation on living organisms, DNA damage is of particular interest[1] and many techniques are being developed to both measure and predict it. The basic DNA elements (2-deoxyribose, phosphate, base) are in Geant[4] often represented by static reactive spheres (or sinks) linked together to form more complex structures, from the nucleotide pair to the genome.[2,3,4,5,6] The reaction mechanism is diffusion-controlled, as it is supposed to be,[7] and triggered when radiolytic species diffuse and encounter a reactive site (generally reactive spheres) that are either representing the sugar-phosphate backbone or the bases of a nucleotide This simple model still ignores the overlap of the reaction sites as well as the overlap of multiple reactive centers in the sugar-base system.[8] it is well suited when focusing on the assessment of the DNA damage on nucleotide or base-pair level

Methods

Results

Conclusion