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

Abstract

Purpose: Simulation 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. Methods: This 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. Results: Results 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. Conclusion: Offering 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.

A Geant4-DNA Evaluation of Radiation-Induced DNA Damage on a Human Fibroblast

“…This idea was initially proposed in previous Geant4-DNA works for the simulation of DNA damage induced by ionizing radiation in E. coli [ 11 , 13 , 28 ]. The entire chemistry simulation through T chem was split into several time steps of maximum duration dt max , and the reaction times are sampled at each time step [ 29 ].…”

Review of the Geant4-DNA Simulation Toolkit for Radiobiological Applications at the Cellular and DNA Level

“…The reaction times are sampled according to the reaction probability, which is calculated by the solution of the Smoluchowski equation (4) with boundary conditions (for totally or partially diffusion-controlled reactions) transformed to radial Green’s function in a spherical coordinate system. The details of the IRT are found elsewhere in [ 100 , 103 , 104 , 105 ]. This approach allows the performance of water radiolysis simulation with reasonable computational time.…”

“…More details about the C++ classes and their structure can be found through the README file of the example. To improve the computation time of the example, the IRT method is currently implemented in this example as an option [ 105 ].…”

Radical Production with Pulsed Beams: Understanding the Transition to FLASH

“…Simulation of the heterogeneous chemical stage of the radiolysis of water often involves the solution of the diffusion or Smoluchowski equation. For this purpose, several stochastic models have been developed, such as the step-by-step (SBS) or the independent time reaction (IRT) methods, which are implemented in the Geant4-DNA and TOPAS-nBio simulation tools [ 59 ]. The SBS method is computationally more expensive but allows for accurate simulations of different biological molecules.…”