A nanodosimetric model of radiation-induced clustered DNA damage yields

Garty, Guy; Schulte, R.; Shchemelinin, S.; Leloup, C.; Assaf, Gad; Breskin, A.; Chechik, R.; Bashkirov, V.; Milligan, Jamie R.; Großwendt, B.

doi:10.1088/0031-9155/55/3/015

Cited by 62 publications

(60 citation statements)

References 46 publications

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“…As long as DNA damage is the main target of the physical component of the GNP radiosensitization, further attention has to be paid to the track structure of the secondary radiation. Recently the nanodosimetry paradigm has been used in order to assess the DNA damage (Grosswendt 2005, Garty et al 2010. Within the nanodosimetry framework the dose deposition profile is not directly considered.…”

Section: Discussionmentioning

confidence: 99%

Geant4 interaction model comparison for dose deposition from gold nanoparticles under proton irradiation

Sotiropoulos

Taylor

Henthorn

et al. 2017

Biomed. Phys. Eng. Express

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Gold nanoparticles (GNPs) have shown a potential as a radiosensitizer in radiotherapy. The radiosensitization effect is thought to be linked to the increased dose deposition around the GNP. Monte Carlo simulations have been implemented for the calculation of the dose distributions around the GNPs and have been used for the calculation of the dose enhancement. They have also been imported to radiobiological models to predict biological endpoints. This work assessed the implications of different physical interaction models on the dose distribution and dose enhancement of GNPs surrounded by water under proton irradiation. The Penelope and Livermore physical interaction model implementation of the Geant4 simulation toolkit were compared considering the following parameters: i) GNP size, ii) proton energy, and iii) alternative physics model parameters in the gold or water medium. We found that neither the dose distribution nor the dose enhancement is sensitive to the model selection after the first 100 nm from the GNP surface. Within the first 100 nm the Livermore models calculated a higher dose, attributed to a higher production of low energy secondary electrons inside the GNP.

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Section: Discussionmentioning

confidence: 99%

Geant4 interaction model comparison for dose deposition from gold nanoparticles under proton irradiation

Sotiropoulos

Taylor

Henthorn

et al. 2017

Biomed. Phys. Eng. Express

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“…A more sophisticated combinatorial approach was proposed by Garty et al (2006, Garty et al 2010 to predict the frequency distribution of DNA strand breaks from the known ionisation cluster size distribution P(ν|Q).…”

Section: Nanodosimetric Estimates Of Biological Effectivenessmentioning

confidence: 99%

“…Interactions of ionising radiation within, or close to, the DNA molecule may result in damage in the form of DNA strand breaks (Bedford 1991, Goodhead et al 1993, Goodhead 2006, Garty et al 2010. Clusters of strand breaks can result in genomic instability, carcinogenesis, and cell death (Goodhead et al 1993, Goodhead 1994.…”

Section: Introductionmentioning

confidence: 99%

Comparison of nanodosimetric parameters of track structure calculated by the Monte Carlo codes Geant4-DNA and PTra

et al. 2012

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The concept of nanodosimetry is based on the assumption that initial damage to cells is related to the number of ionisations (the ionisation cluster size) directly produced by single particles within, or in the close vicinity of, short segments of DNA. The ionisation cluster size distribution and other nanodosimetric quantities, however, are not directly measurable in biological targets and our present knowledge is mostly based on numerical simulations of particle tracks in water, calculating track structure parameters for nanometric target volumes. The assessment of nanodosimetric quantities derived from particle-track calculations using different Monte Carlo codes plays therefore an important role for a more accurate evaluation of the initial damage to cells and, as a consequence, of the biological effectiveness of ionising radiation. The aim of this work is to assess the differences in the calculated nanodosimetric quantities obtained with Geant4-DNA as compared to those of an ad-hoc particle-track Monte Carlo code developed at PTB. The comparison of the two codes was done for incident electrons of energy in the range between 50 eV and 10 keV, for protons of energy between 300 keV and 10 MeV, and for alpha particles of energy between 1 MeV and 10 MeV. Good agreement was found for nanodosimetric characteristics of track structure calculated in the high energy range of each particle type. For lower energies, significant differences were observed, most notably in the estimates of the biological effectiveness The largest relative differences obtained were over 50 %, however generally the order of magnitude was between 10 % and 20 %. P. Lazarakis et al.:Comparison of nanodosimetric parameters of track structure calculated by Geant4-DNA and PTB … 3 / 34

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“…This parameter F 2 has been suggested to be related to the probability for producing a complex lesion within a short segment of DNA (Grosswendt 2005). Furthermore, using the model proposed by Garty et al (Garty et al 2010), the probability P DSB of producing a double strand break was calculated. Briefly, this is done by assuming that each ionisation has a fixed probability (p SB = 11.7 %) of producing a strand break and then using a straightforward combinatorial approach to determine the frequency distribution of DNA strand breaks from the probability distribution of the number of ionisations within the DNA segment volume, as calculated using MC methods.…”

Section: Methodsmentioning

confidence: 99%

“…This was done by simulating electron, proton and alpha particle tracks and calculating nanodosimetric parameters related to the particle track structure (Grosswendt et al 2007). Furthermore, the model proposed by Garty et al (Garty et al 2010) was used to estimate the probability of producing a double strand break. Changes to the calculated values of these parameters induced by the application of a magnetic field may indicate a change to the biological effectiveness of the radiation.…”

Section: Introductionmentioning

confidence: 99%

Effect of a static magnetic field on nanodosimetric quantities in a DNA volume

Lazarakis

Bug

Gargioni

et al. 2011

International Journal of Radiation Biology

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Short title: Effect of a magnetic field on track structure Index Terms: Radiotherapy, nanodosimetry, magnetic field, secondary electrons, Geant4, Monte Carlo, cluster size Abstract Purpose: With the advent of MRI (magnetic resonance imaging) guided radiation therapy it is becoming increasingly important to consider the potential influence of a magnetic field on ionising radiation. This paper aims to study the effect of a magnetic field on the track structure of radiation to determine if the biological effectiveness may be altered.Methods: Using the Geant4-DNA (GEometry ANd Tracking 4) Monte Carlo simulation toolkit, nanodosimetric track structure parameters were calculated for electrons, protons and alpha particles moving in transverse magnetic fields up to 10 Tesla. Applying the model proposed by Garty et al. the track structure parameters were used to derive the probability of producing a double strand break (DSB).Results: For simulated primary particles of electrons (200 eV -10 keV), protons (300 keV -30 MeV) and alpha particles (1 MeV -9 MeV) the application of a magnetic field was shown to have no significant effect (within statistical uncertainty limits) on the parameters characterising radiation track structure or the probability of producing a DSB.Conclusions: The null result found here implies that if the presence of a magnetic field were to induce a change in the biological effectiveness of radiation, the effect would likely not be due to a change in the track structure of the radiation.

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A nanodosimetric model of radiation-induced clustered DNA damage yields

Cited by 62 publications

References 46 publications

Geant4 interaction model comparison for dose deposition from gold nanoparticles under proton irradiation

Geant4 interaction model comparison for dose deposition from gold nanoparticles under proton irradiation

Comparison of nanodosimetric parameters of track structure calculated by the Monte Carlo codes Geant4-DNA and PTra

Effect of a static magnetic field on nanodosimetric quantities in a DNA volume

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