Calculation of the initial DNA damage induced by alpha particles in comparison with protons and electrons using Geant4-DNA

Moeini, H.; Mokari, Mojtaba; Alamatsaz, M H; Taleei, Reza

doi:10.1080/09553002.2020.1730015

Cited by 14 publications

(17 citation statements)

References 45 publications

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“…The bottom panel shows the ratio of our SSB and DSB yields, in comparison with PARTRAC and Geant4‐DNA proton results of Sakata et al 55 . as well as the results extracted from our previous studies for protons 16 and alpha particles 17 …”

Section: Resultsmentioning

confidence: 79%

“…The SSB frequency rose with energy and peaked around 64 MeV/u before it fell back with a slower rate. This can be compared with alpha particles up to 5 MeV/u, 17 for which the SSB frequency (again, as opposed to other damage types) increased appreciably, whereas the DSB, DSB + , and DSB ++ frequencies declined and the SSB + and 2SSB frequencies remained indifferent with energy. Based on the SSB + and DSB + results, for carbon-ion energies below 16 MeV/u, it was considerably less probable to break only one strand at two positions than to break the other strand as well at a third position less than 10 bp away from one of the two breaks on the first strand.…”

Section: Discussionmentioning

confidence: 98%

“…The solid and long-dashed curves are polynomial fits to the ratio of the corresponding data points in the upper two panels. For comparison, our results for protons 16 and alpha particles 17 are shown as dotted and dot-dashed curves, respectively. DSB, double-strand break; SSB, single-strand break and Pater et al, 54 which were derived using PARTRAC and Geant4-DNA.…”

Section: Discussionmentioning

confidence: 99%

“…45 Different types of the resulting DNA SB are depicted in Figure 1. Details of damage calculation and classi-fication were described in Moeini et al, 17 explaining the criteria for registering an SB originated from a physical or chemical process. Hence, a threshold of 17.5 eVcalculated by Martin and Haseltine 46 through modeling the experimental data of 125 I and confirmed later by Kandaiya et al 47 through substantial analyses-was to be satisfied for registering an SB as a direct damage.…”

Section: Methodsmentioning

confidence: 99%

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DNA damage and microdosimetry for carbon ions: Track structure simulations as the key to quantitative modeling of radiation‐induced damage

Moeini

Mokari²

2022

Medical Physics

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Purpose Dose distribution in carbon‐ion irradiations is generally envisaged to have therapeutic advantages over protons, primarily due to the carbon ion's comparatively higher relative biological effectiveness in the tumor than in the encompassing healthy tissues. The objective of this work was to simulate the overall physical and chemical reactions of primary carbon ions impinging on liquid water and, as such, to investigate the DNA‐damage yields in the form of strand breaks (SBs) and in connection with the expected microdosimetric quantities. Materials and methods Using a B‐DNA model and Geant4‐DNA, we simulated the primary and secondary interactions in a spherical medium of water. Subsequently, we categorized DNA damages based on their complexity utilizing the concept of μ‐randomness. We assumed a threshold of 17.5 eV for a direct SB and a probability of 0.13 for an indirect SB triggered by chemical reactions of hydroxyl radicals. Microdosimetric quantities were extracted for three cylindrical volumes representing typical subcellular organisms. Results For fully ionized carbons of 8–256 MeV/u, the yield results appeared to be considerably influenced by the chemical reactions—indicating the important role of secondary electrons in inflicting damage. However, it was mostly the direct‐damage spectrum that determined the overall shape of the damage spectrum. At all primary energies, it was more probable to break each DNA strand at one point—the two points being less than 10 bp apart—than to break only one strand at two random points. Unlike proton's mean‐specific‐energy results, which showed more sensitivity to the volume increase of the smallest cylinder than of the larger ones, carbon‐ion results showed no such sensitivity. Conclusion The growth of the yield ratio of the single‐ and double‐strand breaks (DSB) with the particle energy was estimated for protons to be about 2 times that of alphas and 92 times that of carbon ions. Unlike the proton results, which suggested significant correlations between the DSB yields and mean‐specific (and lineal) energies, carbon ions exhibited no such correlations.

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Section: Resultsmentioning

confidence: 79%

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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DNA damage and microdosimetry for carbon ions: Track structure simulations as the key to quantitative modeling of radiation‐induced damage

Moeini

Mokari²

2022

Medical Physics

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“…Relationship between LET and the initial alpha-particle energy for simulated datasets in the energy range 5-10 MeV. (Friedland et al 2005(Friedland et al , 2011(Friedland et al , 2017de la Fuente Rosales et al 2018;Moeini et al 2020). A total of 23 (40%) datapoints are in the 94 þ5 À5 -192 þ15 À18 keV/mm LET range estimated by the MC study for radon-222 and its progeny in the secretory cell nuclei targets.…”

Section: Simulation Of Lung Secretory Cell Targetmentioning

confidence: 99%

Challenges in the quantification approach to a radiation relevant adverse outcome pathway for lung cancer

Stainforth

Schuemann

McNamara

et al. 2020

International Journal of Radiation Biology

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Purpose: Adverse outcome pathways (AOPs) provide a modular framework for describing sequences of biological key events (KEs) and key event relationships (KERs) across levels of biological organization. Empirical evidence across KERs can support construction of quantified AOPs (qAOPs). Using an example AOP of energy deposition from ionizing radiation onto DNA leading to lung cancer incidence, we investigate the feasibility of quantifying data from KERs supported by all types of stressors. The merits and challenges of this process in the context of AOP construction are discussed. Materials and methods: Empirical evidence across studies of dose-response from four KERs of the AOP were compiled independently for quantification. Three upstream KERs comprised of evidence from various radiation types in line with AOP guidelines. For these three KERs, a focused analysis of data from alpha-particle studies was undertaken to better characterize the process to the adverse outcome (AO) for a radon gas stressor. Numerical information was extracted from tables and graphs to plot and tabulate the response of KEs. To complement areas of the AOP quantification process, Monte Carlo (MC) simulations in TOPAS-nBio were performed to model exposure conditions relevant to the AO for an example bronchial compartment of the lung with secretory cell nuclei targets. Results: Quantification of AOP KERs highlighted the relevance of radiation types under the stressor-agnostic intent of AOP design, motivating a focus on specific types. For a given type, significant differences of KE response indicate meaningful data to derive linkages from the MIE to the AO is lacking and that better response-response focused studies are required. The MC study estimates the linear energy transfer (LET) of alpha-particles emitted by radon-222 and its progeny in the secretory cell nuclei of the example lung compartment to range from 94 þ5 À5 to 192 þ15 À18 keV/mm. Conclusion:Quantifying AOP components provides a means to assemble empirical evidence across different studies. This highlights challenges in the context of studies examining similar endpoints using different radiation types. Data linking KERs to a MIE of 'deposition of energy' is shown to be non-compatible with the stressor-agnostic principles of AOP design. Limiting data to that describing response-response relationships between adjacent KERs may better delineate studies relevant to the damage that drives a pathway to the next KE and still support an 'all hazards' approach. Such data remains limited and future investigations in the radiation field may consider this approach when designing experiments and reporting their results and outcomes.

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In-silico calculations of DNA damage induced by α-particles in the 224Ra DaRT decay chain for a better understanding of the radiobiological effectiveness of this treatment

et al. 2023

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Calculation of the initial DNA damage induced by alpha particles in comparison with protons and electrons using Geant4-DNA

Cited by 14 publications

References 45 publications

DNA damage and microdosimetry for carbon ions: Track structure simulations as the key to quantitative modeling of radiation‐induced damage

DNA damage and microdosimetry for carbon ions: Track structure simulations as the key to quantitative modeling of radiation‐induced damage

Challenges in the quantification approach to a radiation relevant adverse outcome pathway for lung cancer

In-silico calculations of DNA damage induced by α-particles in the 224Ra DaRT decay chain for a better understanding of the radiobiological effectiveness of this treatment

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