IDDRRA: A novel platform, based on Geant4‐DNA to quantify DNA damage by ionizing radiation

Chatzipapas, Konstantinos; Papadimitroulas, Panagiotis; Loudos, George; Papanikolaou, Niko; Kagadis, George C.

doi:10.1002/mp.14817

Cited by 9 publications

(8 citation statements)

References 64 publications

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“…The more complex the initial damage to DNA, the higher the probability of being mis-repaired and thus consequences on cell fate can be expected. Therefore, modelling of early damage to DNA represents a powerful tool to predict irradiation risk [ 109 ]. This is only possible if a detailed understanding of the mechanisms of ionizing radiation action on living organisms is implemented in the code.…”

Section: Towards the Modelling Of Early Dna Damagementioning

confidence: 99%

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

Kyriakou

Sakata

Tran

et al. 2021

Cancers

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The Geant4-DNA low energy extension of the Geant4 Monte Carlo (MC) toolkit is a continuously evolving MC simulation code permitting mechanistic studies of cellular radiobiological effects. Geant4-DNA considers the physical, chemical, and biological stages of the action of ionizing radiation (in the form of x- and γ-ray photons, electrons and β±-rays, hadrons, α-particles, and a set of heavier ions) in living cells towards a variety of applications ranging from predicting radiotherapy outcomes to radiation protection both on earth and in space. In this work, we provide a brief, yet concise, overview of the progress that has been achieved so far concerning the different physical, physicochemical, chemical, and biological models implemented into Geant4-DNA, highlighting the latest developments. Specifically, the “dnadamage1” and “molecularDNA” applications which enable, for the first time within an open-source platform, quantitative predictions of early DNA damage in terms of single-strand-breaks (SSBs), double-strand-breaks (DSBs), and more complex clustered lesions for different DNA structures ranging from the nucleotide level to the entire genome. These developments are critically presented and discussed along with key benchmarking results. The Geant4-DNA toolkit, through its different set of models and functionalities, offers unique capabilities for elucidating the problem of radiation quality or the relative biological effectiveness (RBE) of different ionizing radiations which underlines nearly the whole spectrum of radiotherapeutic modalities, from external high-energy hadron beams to internal low-energy gamma and beta emitters that are used in brachytherapy sources and radiopharmaceuticals, respectively.

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Section: Towards the Modelling Of Early Dna Damagementioning

confidence: 99%

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

Kyriakou

Sakata

Tran

et al. 2021

Cancers

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“…Thus, track-structure Monte Carlo (MC) simulations have an important role in investigating DNA damage induced after radiation irradiation [ 9 , 10 , 11 ]. In the past decades, many MC codes have achieved successful outcomes for quantitative investigation of radiation-induced initial DNA damage within cellular domains and subcellular biological components [ 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ].…”

Section: Introductionmentioning

confidence: 99%

Performance Evaluation for Repair of HSGc-C5 Carcinoma Cell Using Geant4-DNA

Sakata

Suzuki²,

Hirayama³

et al. 2021

Cancers

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Track-structure Monte Carlo simulations are useful tools to evaluate initial DNA damage induced by irradiation. In the previous study, we have developed a Gean4-DNA-based application to estimate the cell surviving fraction of V79 cells after irradiation, bridging the gap between the initial DNA damage and the DNA rejoining kinetics by means of the two-lesion kinetics (TLK) model. However, since the DNA repair performance depends on cell line, the same model parameters cannot be used for different cell lines. Thus, we extended the Geant4-DNA application with a TLK model for the evaluation of DNA damage repair performance in HSGc-C5 carcinoma cells which are typically used for evaluating proton/carbon radiation treatment effects. For this evaluation, we also performed experimental measurements for cell surviving fractions and DNA rejoining kinetics of the HSGc-C5 cells irradiated by 70 MeV protons at the cyclotron facility at the National Institutes for Quantum and Radiological Science and Technology (QST). Concerning fast- and slow-DNA rejoining, the TLK model parameters were adequately optimized with the simulated initial DNA damage. The optimized DNA rejoining speeds were reasonably agreed with the experimental DNA rejoining speeds. Using the optimized TLK model, the Geant4-DNA simulation is now able to predict cell survival and DNA-rejoining kinetics for HSGc-C5 cells.

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“…At the subcellular scale, Monte Carlo simulations have proven to be useful for the quantification and assessment of radiation-induced damage, particularly to the DNA molecule. Several tools are currently available, such as PARTRAC, 10 KURBUC, 11 and RITRACKS 12 , Geant4-DNA, [13][14][15][16] gMicroMC, 17,18 TOPAS-nBIO, 19,20 MPEXS-DNA, 21 and IDDRRA, 22 that either are based on Geant4-DNA or include some of its features. Kyriakou et al carried out a review of such tools.…”

Section: Introductionmentioning

confidence: 99%

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

Chatzipapas

Tran

Dordevic³

et al. 2023

Precision Radiation Oncology

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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.

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IDDRRA: A novel platform, based on Geant4‐DNA to quantify DNA damage by ionizing radiation

Cited by 9 publications

References 64 publications

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

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

Performance Evaluation for Repair of HSGc-C5 Carcinoma Cell Using Geant4-DNA

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

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