Simulation of DNA damage using Geant4‐DNA: an overview of the “molecularDNA” example application

Abstract

Purpose:The scientific community shows great interest in the study of DNA damage induction, DNA damage repair, and the biological effects on cells and cellular systems after exposure to ionizing radiation. Several in silico methods have been proposed so far to study these mechanisms using Monte Carlo simulations. This study outlines a Geant4-DNA example application, named "molecularDNA", publicly released in the 11.1 version of Geant4 (December 2022).Methods: It was developed for novice Geant4 users and requires only a basic understanding of scripting languages to get started. The example includes two different DNA-scale geometries of biological targets, namely "cylinders" and "human cell". This public version is based on a previous prototype and includes new features, such as: the adoption of a new approach for the modeling of the chemical stage, the use of the standard DNA damage format to describe radiation-induced DNA damage, and upgraded computational tools to estimate DNA damage response.Results: Simulation data in terms of single-strand break and double-strand break yields were produced using each of the available geometries. The results were compared with the literature, to validate the example, producing less than 5% difference in all cases.Conclusion: "molecularDNA" is a prototype tool that can be applied in a wide variety of radiobiology studies, providing the scientific community with an open-access base for DNA damage quantification calculations. New DNA and cell geometries for the "molecularDNA" example will be included in future versions of Geant4-DNA.

Simulation of DNA damage using the “molecularDNA” example application of Geant4-DNA

“…It enables the simulation of the direct and non-direct early DNA damage induction and a quantitative measure of this damage through counting the number of single strand breaks, SSB, DSB and DNA fragments distribution. The "human cell" geometrical configuration was irradiated with protons of energies in the range of 0.15 to 66.5 MeV, corresponding to the LET range from 73.5 to 1 keV/μm and both SSB and DSB yields, as well as their ratio, were calculated [1]. The SSB/DSB ratio, the DNA fragment length frequency distribution for 1 MeV incident protons, the damage kinetics as a function of DNA repair time and also the surviving fraction curves of NB1RGB cells as a function of delivered dose are also reported in [1].…”

“…The "human cell" geometrical configuration was irradiated with protons of energies in the range of 0.15 to 66.5 MeV, corresponding to the LET range from 73.5 to 1 keV/μm and both SSB and DSB yields, as well as their ratio, were calculated [1]. The SSB/DSB ratio, the DNA fragment length frequency distribution for 1 MeV incident protons, the damage kinetics as a function of DNA repair time and also the surviving fraction curves of NB1RGB cells as a function of delivered dose are also reported in [1]. The lung carcinoma, HTB-177, and breast adenocarcinoma MCF-7, cancer cell lines were modelled and incorporated into the "molecularDNA" example, starting from the default "human cell" geometry.…”

ICRU Report 98, Stochastic Nature of Radiation Interactions: Microdosimetry

“…The Geant4-DNA platform has since been applied in many studies of damage to the DNA molecule and its higher-order structures in mammalian cells (Figs. 9.17 and 9.18) and other organisms exposed to many radiation types, including those of interest in radiotherapy, space travel, and radiobiology (Chatzipapas et al , 2020; 2021; 2023; Dominguez-Kondo et al , 2021; Dos Santos et al , 2020; Henthorn et al , 2017; Hilgers et al , 2022; Incerti et al , 2016; 2020; Kyriakou et al , 2021; 2022; Lee and Wang, 2019; Margis et al , 2020; Moeini et al , 2020; Mokari et al , 2020; Sakata et al , 2019; Tang et al , 2020; Thibault et al , 2022; Thompson et al , 2022). Development of the Geant4-DNA platform for radiobiological applications included incorporation of a feature allowing for prediction of DNA rejoining kinetics and corresponding cell surviving fraction as a function of time.…”

Assessment of Annual Effective Dose and Excess Lifetime Cancer Risk Due to Natural Background Radiation Levels in West Pokot, Kenya

“…This damage extends to DNA, resulting in base damage, sugar damage, single-strand breaks (SSBs), double-strand breaks (DSBs), and DNA-protein cross-links (Collins & Azqueta, 2014;Islam, 2017). DNA damage contributes to gene mutation, chromosomal anomalies, cell death, mutagenesis, and carcinogenesis, often leading to chronic diseases and various types of cancer (Avwiri et al, 2017;Chatzipapas et al, 2023;Kaur et al, 2019;Qureshi et al, 2014). Considering these health implications, cancer remains a signi cant adverse outcome associated with ionizing radiation exposure, highlighting the need for a thorough investigation and mitigation of potential environmental consequences that address ecological and health concerns.…”