Modeling Dna Damage by Photons and Light Ions Over Energy Ranges Used in Medical Applications

Friedland, W.; Kundrát, Pavel; Schmitt, E.; Becker, J; Li, Wei Bo

doi:10.1093/rpd/ncy245

Cited by 10 publications

(23 citation statements)

References 6 publications

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“…When the specific DNA damage type under consideration shows a linear dependence on radiation dose, as is the case here, the RBE (formally defined as the ratio of doses at the same effect) is simply given by the ratio of damage yields at the same dose. As done previously 11 , the simulation results for low-LET hydrogen ions can be used as a reference; indeed, their damage induction is in line with that by reference photon irradiations 12 . This allows a quick RBE calculation for DNA damage induction with the presented formulas.…”

Section: Discussionsupporting

confidence: 74%

“…* email: giorgio.baiocco@unipv.it irradiation setup. A spherical model of human lymphocyte nuclei (10 µm diameter) containing 6.6 Gbp DNA in 23 chromosome pairs, corresponding to the interphase (G0/G1) cell cycle phase, was in-silico irradiated by 1 H, 4 He, 7 Li, 9 Be, 11 B, 12 C, 14 N, 16 O or 20 Ne ions. The ions were started from random locations within a circular source (10.09 µm diameter) tangential to the cell nucleus, with directions perpendicular to the source plane.…”

Section: Track Structure Based Simulations Valuably Complement Experimentioning

confidence: 99%

“…PARTRAC belongs to the most advanced track-structure tools 5 – 12 . It uses established cross-section databases for photons, electrons, protons and ions over wide energy ranges relevant for medical, biological and technical applications.…”

Section: Introductionmentioning

confidence: 99%

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Analytical formulas representing track-structure simulations on DNA damage induced by protons and light ions at radiotherapy-relevant energies

Kundrát

Friedland

Becker

et al. 2020

Sci Rep

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Track structure based simulations valuably complement experimental research on biological effects of ionizing radiation. They provide information at the highest level of detail on initial DNA damage induced by diverse types of radiation. Simulations with the biophysical Monte Carlo code PARTRAC have been used for testing working hypotheses on radiation action mechanisms, for benchmarking other damage codes and as input for modelling subsequent biological processes. To facilitate such applications and in particular to enable extending the simulations to mixed radiation field conditions, we present analytical formulas that capture PARTRAC simulation results on DNA single- and double-strand breaks and their clusters induced in cells irradiated by ions ranging from hydrogen to neon at energies from 0.5 GeV/u down to their stopping. These functions offer a means by which radiation transport codes at the macroscopic scale could easily be extended to predict biological effects, exploiting a large database of results from micro-/nanoscale simulations, without having to deal with the coupling of spatial scales and running full track-structure calculations.

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Section: Discussionsupporting

confidence: 74%

Section: Track Structure Based Simulations Valuably Complement Experimentioning

confidence: 99%

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Analytical formulas representing track-structure simulations on DNA damage induced by protons and light ions at radiotherapy-relevant energies

Kundrát

Friedland

Becker

et al. 2020

Sci Rep

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“…The limited energies of secondary electrons with a maximum of about 4 keV confines the energy deposit close to the alpha particle trajectory: 55% are located within 1 nm, ~ 90% within 10 nm radial distance. Both these issues lead to an unexcelled effectiveness of alpha particle radiation in producing DSB sites (Friedland et al 2017(Friedland et al , 2018; more densely ionizing radiation by heavier ions is supposed to yield overkill effects.…”

Section: Alpha Particle Tracks In Silico: From Nanoscale To Microscalementioning

confidence: 99%

Internal microdosimetry of alpha-emitting radionuclides

Hofmann

Friedland

et al. 2019

Radiat Environ Biophys

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At the tissue level, energy deposition in cells is determined by the microdistribution of alpha-emitting radionuclides in relation to sensitive target cells. Furthermore, the highly localized energy deposition of alpha particle tracks and the limited range of alpha particles in tissue produce a highly inhomogeneous energy deposition in traversed cell nuclei. Thus, energy deposition in cell nuclei in a given tissue is characterized by the probability of alpha particle hits and, in the case of a hit, by the energy deposited there. In classical microdosimetry, the randomness of energy deposition in cellular sites is described by a stochastic quantity, the specific energy, which approximates the macroscopic dose for a sufficiently large number of energy deposition events. Typical examples of the alpha-emitting radionuclides in internal microdosimetry are radon progeny and plutonium in the lungs, plutonium and americium in bones, and radium in targeted radionuclide therapy. Several microdosimetric approaches have been proposed to relate specific energy distributions to radiobiological effects, such as hit-related concepts, LET and track length-based models, effect-specific interpretations of specific energy distributions, such as the dual radiation action theory or the hit-size effectiveness function, and finally track structure models. Since microdosimetry characterizes only the initial step of energy deposition, microdosimetric concepts are most successful in exposure situations where biological effects are dominated by energy deposition, but not by subsequently operating biological mechanisms. Indeed, the simulation of the combined action of physical and biological factors may eventually require the application of track structure models at the nanometer scale.

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“…For all the above reasons, state-of-the-art MCTS biophysical codes, like PARTRAC and KURBUC, are still using liquid water as an approximation to the biological medium and have been particularly successful in simulating biological damage induced by ionising radiation. 3,27 For these reasons, all simulations presented in this work use liquid water as an approximation for the biological medium.…”

Section: Introductionmentioning

confidence: 99%

Track structure simulations of proximity functions in liquid water using the Geant4-DNA toolkit

Incerti

Kyriakou

Bordage

et al. 2019

Journal of Applied Physics

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The mechanistic Monte Carlo modeling of biological effects of ionising radiation at sub-cellular and DNA scale requires the accurate simulation of track structures in the biological medium, commonly approximated as liquid water. The formalism of microdosimetry allows one to describe quantitatively the spatial distribution of energy deposition in the irradiated medium, which is known to relate to the deleterious effects in the irradiated cellular targets. The Geant4-DNA extension of the Geant4 opensource and general-purpose Monte Carlo simulation toolkit has been recently evaluated for the simulation of microdosimetry spectra, allowing, in particular, the calculation of lineal energy distributions. In this work, we extend the microdosimetric functionalities of Geant4-DNA by the development of a new Geant4-DNA example dedicated to the simulation of differential proximity functions. Simulation results are presented for the proximity function of electrons, protons, and alpha particles over a wide energy range using the different physical models of electron interactions available in Geant4-DNA. The influence of sub-excitation processes and electron tracking cut is discussed. Results are compared to literature data when available. As an example, a simple calculation of the relative biological effectiveness (RBE) in the context of the Theory of Dual Radiation Action using the present proximity functions yields up to a factor of 2 variation of the electron RBE in the energy range from 100 eV to 100 keV.

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Modeling Dna Damage by Photons and Light Ions Over Energy Ranges Used in Medical Applications

Cited by 10 publications

References 6 publications

Analytical formulas representing track-structure simulations on DNA damage induced by protons and light ions at radiotherapy-relevant energies

Analytical formulas representing track-structure simulations on DNA damage induced by protons and light ions at radiotherapy-relevant energies

Internal microdosimetry of alpha-emitting radionuclides

Track structure simulations of proximity functions in liquid water using the Geant4-DNA toolkit

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