Monte Carlo simulation of early biological damage induced by ionizing radiation at the DNA scale: Overview of the Geant4-DNA project

Modeling accurately biological damage induced by ionizing radiation at the scale of the DNA molecule remains a major challenge of today’s radiobiology research (1). In order to provide the community with an easily accessible mechanistic simulation platform, the general purpose and open source “Geant4” particle-matter Monte Carlo simulation toolkit (2) is being extended in the framework of the “Geant4-DNA” project (3-7) with a set of functionalities allowing the detailed simulation of particle-matter interactions in biological medium. These functionalities include physical, physico-chemical and chemical processes that can be combined with nanometer size geometries of biological targets in order to predict early DNA damage. We will present an overview of the Geant4-DNA project and discuss on-going developments.VII International Conference on Radiation in Various Fields of Research : RAD 2019 : book of abstracts; June 10-14, 2019; Herceg Novi, Montenegr

Microdosimetry of electrons in liquid water using the low-energy models of Geant4

The biological effects of ionizing radiation at the cellular level are frequently studied using the well-known formalism of microdosimetry, which provides a quantitative description of the stochastic aspects of energy deposition in irradiated media. Energy deposition can be simulated using Monte Carlo codes, some adopting a computationally efficient condensed-history approach, while others follow a more detailed track-structure approach. In this work, we present the simulation of microdosimetry spectra and related quantities (frequency-mean and dose-mean lineal energies) for incident monoenergetic electrons (50 eV-10 keV) in spheres of liquid water with dimensions comparable to the size of biological targets: base pairs (2 nm diameter), nucleosomes (10 nm), chromatin fibres (30 nm) and chromosomes (300 nm). Simulations are performed using the condensed-history low-energy physics models ( Livermore and Penelope ) and the track-structure Geant4-DNA physics models, available in the Geant4 Monte Carlo simulation toolkit. The spectra are compared and the influence of simulation parameters and different physics models, with emphasis on recent developments, is discussed, underlining the suitability of Geant4-DNA models for microdosimetry simulations. It is further shown that with an appropriate choice of simulation parameters, condensed-history transport may yield reasonable results for sphere sizes as small as a few tens of a nanometer

An implementation of discrete electron transport models for gold in the Geant4 simulation toolkit

Gold nanoparticle (GNP) boosted radiation therapy can enhance the biological effectiveness of radiation treatments by increasing the quantity of direct and indirect radiation-induced cellular damage. As the physical effects of GNP boosted radiotherapy occur across energy scales that descend down to 10 eV, Monte Carlo simulations require discrete physics models down to these very low energies in order to avoid underestimating the absorbed dose and secondary particle generation. Discrete physics models for electron transportation down to 10 eV have been implemented within the Geant4-DNA low energy extension of Geant4. Such models allow the investigation of GNP effects at the nanoscale. At low energies, the new models have better agreement with experimental data on the backscattering coefficient, and they show similar performance for transmission coefficient data as the Livermore and Penelope models already implemented in Geant4. These new models are applicable in simulations focussed towards estimating the relative biological effectiveness of radiation in GNP boosted radiotherapy applications with photon and electron radiation sources

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

The scientific community has a large interest in the studies of DNA damage and response after exposure to ionizing radiation. Several in-silico methods have been proposed so far to model and study the mechanisms of DNA damage using Monte Carlo simulations. The “molecularDNA” example is one of the most recent applications to simulate the irradiation of human cancer cells and bacteria using Geant4-DNA. This example enables the simulation of the physical, physico-chemical and chemical stages of liquid water irradiation, including radiolytic processes following the particle irradiation of the pre-defined human cell geometries and it can be used to calculate the early direct and non-direct DNA damage such as single (SSB) and double strand breaks (DSB) as well as DNA fragment distribution. The application is user friendly and can be used following simple macro commands. The results of the Monte Carlo simulation are compared to experimental data of DSB yields, as well as with previously published simulation data.ICCBIKG 2023 : 2nd International Conference on Chemo and Bioinformatics, September 28-29, 2023; Kragujeva

Medical Physics: forming and testing solutions to clinical problems

According to the European Federation of Organizations for Medical Physics (EFOMP) policy statement No. 13, “The rapid advance in the use of highly sophisticated equipment and procedures in the medical field increasingly depends on information and communication technology. In spite of the fact that the safety and quality of such technology is vigorously tested before it is placed on the market, it often turns out that the safety and quality is not sufficient when used under hospital working conditions. To improve safety and quality for patient and users, additional safeguards and related monitoring, as well as measures to enhance quality, are required. Furthermore a large number of accidents and incidents happen every year in hospitals and as a consequence a number of patients die or are injured. Medical Physicists are well positioned to contribute towards preventing these kinds of events”. The newest developments related to this increasingly important medical speciality were presented during the 8th European Conference of Medical Physics 2014 which was held in Athens, 11–13 September 2014 and hosted by the Hellenic Association of Medical Physicists (HAMP) in collaboration with the EFOMP and are summarized in this issue

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

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