Comprehensive track-structure based evaluation of DNA damage by light ions from radiotherapy-relevant energies down to stopping

Friedland, W.; Schmitt, E.; Kundrát, Pavel; Dingfelder, M.; Baiocco, G.; Barbieri, Sofia; Ottolenghi, A.

doi:10.1038/srep45161

Cited by 163 publications

(249 citation statements)

References 63 publications

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“…In the present study, we simulated only the physical stage of the interactions (i.e., the direct effect of ionizing radiation), as a result of which we did not calculate absolute numbers of DNA breaks. Thus, our results cannot be directly compared to DNA break yields published in previous MC studies . Moreover, most of these studies focused on charged particles (i.e., protons, alpha particles and heavier ions) with specific LET and for which the sources were delivered directly to the cell nucleus.…”

Section: Discussionmentioning

confidence: 98%

“…In the last decades, several cell nuclei models containing DNA geometry have been implemented in MC simulations to quantify DNA damage and to aid understanding of their biological effects. Different MC codes (e.g., KURBUC or PARTRAC), geometry models, DNA break quantification methods and, for the most advanced codes, DNA repair processes have been used in calculations aiming of quantifying DNA damage . In the present study, we simulated only the physical stage of the interactions (i.e., the direct effect of ionizing radiation), as a result of which we did not calculate absolute numbers of DNA breaks.…”

Section: Discussionmentioning

confidence: 99%

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Minibeam radiation therapy: A micro‐ and nano‐dosimetry Monte Carlo study

et al. 2020

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Purpose Minibeam radiation therapy (MBRT) is an innovative strategy based on a distinct dose delivery method that is administered using a series of narrow (submillimetric) parallel beams. To shed light on the biological effects of MBRT irradiation, we explored the micro‐ and nanodosimetric characteristics of three promising MBRT modalities (photon, electron, and proton) using Monte Carlo (MC) calculations. Methods Irradiation with proton (100 MeV), electron (300 MeV), and photon (effective energy of 69 keV) minibeams were simulated using Geant4 MC code and the Geant4‐DNA extension, which allows the simulation of energy transfer points with nanometric accuracy. As the target of the simulations, cells containing spherical nuclei with or without a detailed description of the DNA (deoxyribonucleic acid) geometry were placed at different depths in peak and valley regions in a water phantom. The energy deposition and number of events in the cell nuclei were recorded in the microdosimetry study, and the number of DNA breaks and their complexity were determined in the nanodosimetric study, where a multi‐scale simulation approach was used for the latter. For DNA damage assessment, an adapted DBSCAN clustering algorithm was used. To compare the photon MBRT (xMBRT), electron MBRT (eMBRT), and proton MBRT (pMBRT) approaches, we considered the treatment of a brain tumor located at a depth of 75 mm. Results Both mean energy deposition at micrometric scale and DNA damage in the “valley” cell nuclei were very low as compared with these parameters in the peak region at all depths for xMBRT and at depths of 0 to 30 mm and 0 to 50 mm for eMBRT and pMBRT, respectively. Only the charged minibeams were favorable for tumor control by producing similar effects in peak and valley cells after 70 mm. At the micrometer scale, the energy deposited per event pointed to a potential advantage of proton beams for tumor control, as more aggressive events could be expected at the end of their tracks. At the nanometer scale, all three MBRT modalities produced direct clustered DNA breaks, although the majority of damage (>93%) was composed of isolated single strand breaks. The pMBRT led to a significant increase in the proportion of clustered single strand breaks and double‐strand breaks at the end of its range as compared to the entrance (7% at 75 mm vs 3% at 10 mm) in contrast to eMBRT and xMBRT. In the latter cases, the proportions of complex breaks remained constant, irrespective of the depth and region (peak or valley). Conclusions Enhanced normal tissue sparing can be expected with these three MBRT techniques. Among the three modalities, pMBRT offers an additional gain for radioresistant tumors, as it resulted in a higher number of complex DNA damage clusters in the tumor region. These results can aid understanding of the biological mechanisms of MBRT.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Minibeam radiation therapy: A micro‐ and nano‐dosimetry Monte Carlo study

et al. 2020

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“…It must be emphasized that most of the existing track structure codes have not yet addressed the problem of the influence of chromatin compaction on the simulation. To the best of authors’ knowledge, only the PARTRAC code has already implemented hetero‐ and euchromatin structures in previous work . Unfortunately, this publication focused on the PARTRAC's repair module, and the results mainly concern chromosomal aberration yields; thus, no results on the influence of chromatin compaction on early DNA damage were obtained to allow for further comparisons.…”

Section: Discussionmentioning

confidence: 99%

Influence of chromatin compaction on simulated early radiation‐induced DNA damage using Geant4‐DNA

Tang

Bueno

Meylan³

et al. 2019

Medical Physics

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Purpose In this work, we present simulated double‐strand breaks (DSBs) obtained for two human cell nucleus geometries. The first cell nucleus represents fibroblasts, filled with DNA molecules in different compaction forms: heterochromatin or euchromatin only. The second one represents an endothelial cell nucleus, either filled with heterochromatin only or with a uniform distribution of 48% of heterochromatin and 52% of euchromatin, obtained from measurements carried out at IRSN. Protons and alpha particles of different energies were used as projectiles. Each cell nucleus model includes a multi‐scale description of the DNA target from the molecular level to the whole human genome representation. Methods The cell nucleus models were generated using an extended version of the DnaFabric software in which a new model of euchromatin was implemented in addition to the existing model of heterochromatin. Thus, each nucleus model contains the complete human genome (a total of 6 Gbp) in the G0/G1 phase of the cycle, filled with a continuous chromatin fiber per chromosome that can take into account the heterochromatin and the euchromatin compaction. These geometries were then exported to a simulation chain using the Monte Carlo toolkit Geant4‐DNA to perform computations of the physical, physicochemical, and chemical stages, in order to evaluate the influence of chromatin compaction on DSB induction and the contribution of direct and indirect damage, as well as DSB complexity. Results More direct damage and less indirect damage were observed in the heterochromatin than in the euchromatin. Nevertheless, no difference in terms of DSB complexity was observed between those formed in the heterochromatin or the euchromatin models. Yields of DSB/Gy/Gbp show an increase when both heterochromatin and euchromatin models are taken into account, compared to when only heterochromatin is considered. Conclusions The results presented indicate that the chromatin compaction decreases DNA damage generated by ionizing radiation and thus, DNA compaction should be considered for the simulation of DNA repair and other cellular outcomes.

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“…Nevertheless, empirical methods of relating the dose deposited by ions to the biodamage appeared first [8]. The track-structure community is engaged in modeling of the transport and interactions of reactive species in ion's tracks leading to DNA damage by means of Monte Carlo simulations [11][12][13]. However, these methods do not account for all effects that are involved in the scenario of radiation damage and, therefore, important for treatment planning.…”

Section: Introductionmentioning

confidence: 99%

Ion-impact-induced multifragmentation of liquid droplets

2017

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Abstract. An instability of a liquid droplet traversed by an energetic ion is explored theoretically. This instability is brought about by the predicted shock wave induced by the ion. An observation of multifragmentation of small droplets traversed by ions with high linear energy transfer is suggested to demonstrate the existence of shock waves. A number of effects are analysed in effort to find the conditions for such an experiment to be signifying. The presence of shock waves crucially affects the scenario of radiation damage with ions since the shock waves significantly contribute to the thermomechanical damage of biomolecules as well as the transport of reactive species. While the scenario has been upheld by analyses of biological experiments, the shock waves have not yet been observed directly, regardless of a number of ideas of experiments to detect them were exchanged at conferences.

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Comprehensive track-structure based evaluation of DNA damage by light ions from radiotherapy-relevant energies down to stopping

Cited by 163 publications

References 63 publications

Minibeam radiation therapy: A micro‐ and nano‐dosimetry Monte Carlo study

Minibeam radiation therapy: A micro‐ and nano‐dosimetry Monte Carlo study

Influence of chromatin compaction on simulated early radiation‐induced DNA damage using Geant4‐DNA

Ion-impact-induced multifragmentation of liquid droplets

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