Proton-induced direct and indirect damage of plasmid DNA

Vyšín, L.; Brabcová, Kateřina Pachnerová; Štěpán, Václav; Moretto-Capelle, P; Bugler, Béatrix; Legube, Gaëlle; Cafarelli, P.; Casta, Romain; Champeaux, Jean Philippe; Sence, Martine; Vlk, Martin; Wagner, Richard W.; Štursa, Jan; Zach, V.; Incerti, S.; Juha, L.; Davídková, Marie

doi:10.1007/s00411-015-0605-6

Cited by 49 publications

(55 citation statements)

References 44 publications

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“…In this study, we validate TOPAS-nBio by comparing to a previous Monte Carlo study predicting strand breaks in a simple linear DNA segment for several particles types [11] and an experimental study measuring the occurrence of strand breaks within a DNA plasmid from incident protons [12]. …”

Section: Methodsmentioning

confidence: 99%

“…The interactions of protons within the simple plasmid were simulated and compared to the experimental data from Vyšín et al [12]. In the experimental study, SSB and DSB yields in DNA plasmids after proton irradiation were measured.…”

Section: Methodsmentioning

confidence: 99%

“…Here we present the first validation study of TOPAS-nBio using simple DNA strand models. In this study we compare our simulation results to two previously published studies; an early track structure simulation of strand damage in simple linear DNA segments [11] and experimental measurements of strand damage to proton irradiated DNA plasmids [12]. …”

Section: Introductionmentioning

confidence: 97%

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Validation of the radiobiology toolkit TOPAS-nBio in simple DNA geometries

et al. 2017

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Computational simulations offer a powerful tool for quantitatively investigating radiation interactions with biological tissue and can help bridge the gap between physics, chemistry and biology. The TOPAS collaboration is tackling this challenge by extending the current Monte Carlo tool to allow for sub-cellular in silico simulations in a new extension, TOPAS-nBio. TOPAS wraps and extends the Geant4 Monte Carlo simulation toolkit and the new extension allows the modeling of particles down to vibrational energies (~ 2 eV) within realistic biological geometries. Here we present a validation of biological geometries available in TOPAS-nBio, by comparing our results to two previously published studies. We compare the prediction of strand breaks in a simple linear DNA strand from TOPAS-nBio to a published Monte Carlo track structure simulation study. While TOPAS-nBio confirms the trend in strand break generation, it predicts a higher frequency of events below an energy of 17.5 eV compared to the alternative Monte Carlo track structure study. This is due to differences in the physics models used by each code. We also compare the experimental measurement of strand breaks from incident protons in DNA plasmids to TOPAS-nBio simulations. Our results show good agreement of single and double strand breaks predicting a similar increase in the strand break yield with increasing LET.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

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Validation of the radiobiology toolkit TOPAS-nBio in simple DNA geometries

et al. 2017

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“…It is commonly accepted that nanosize lesions, also called complex damages, are the most lethal for the cells. 23 In this work, we quantified the efficacy of 3 nm platinum (Z=78) and 5 nm gadolinium (Z=64) based NPs to amplify nanosize lesions upon fast proton irradiation. The plasmid pBR322 was used as a molecular probe to quantify simple and complex damages in biomolecules.…”

mentioning

confidence: 99%

Improving proton therapy by metal-containing nanoparticles: nanoscale insights

Schlathölter¹,

Eustache²,

Porcel³

et al. 2016

IJN

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The use of nanoparticles to enhance the effect of radiation-based cancer treatments is a growing field of study and recently, even nanoparticle-induced improvement of proton therapy performance has been investigated. Aiming at a clinical implementation of this approach, it is essential to characterize the mechanisms underlying the synergistic effects of nanoparticles combined with proton irradiation. In this study, we investigated the effect of platinum- and gadolinium-based nanoparticles on the nanoscale damage induced by a proton beam of therapeutically relevant energy (150 MeV) using plasmid DNA molecular probe. Two conditions of irradiation (0.44 and 3.6 keV/μm) were considered to mimic the beam properties at the entrance and at the end of the proton track. We demonstrate that the two metal-containing nanoparticles amplify, in particular, the induction of nanosize damages (>2 nm) which are most lethal for cells. More importantly, this effect is even more pronounced at the end of the proton track. This work gives a new insight into the underlying mechanisms on the nanoscale and indicates that the addition of metal-based nanoparticles is a promising strategy not only to increase the cell killing action of fast protons, but also to improve tumor targeting.

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“…The mass per square centimetre quantities used for determining density of dry DNA films are similar to those often used in irradiation studies [57], therefore the lower value should be used in future studies. Furthermore, since it was shown that there is a strong dependence of the sample composition on DNA film formation and thus on its density, interferometric method will be important in characterizing particle interactions with DNA films and the dose dependence [119]. The result presented here also indicates that depending on the film preparation method, i.e.…”

Section: Discussionmentioning

confidence: 51%

Evaluating experimental molecular physics studies of radiation damage in DNA*

Śmiałek

2016

Eur. Phys. J. D

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Abstract. The field of Atomic and Molecular Physics (AMP) is a mature field exploring the spectroscopy, excitation, ionisation of atoms and molecules in all three phases. Understanding of the spectroscopy and collisional dynamics of AMP has been fundamental to the development and application of quantum mechanics and is applied across a broad range of disparate disciplines including atmospheric sciences, astrochemistry, combustion and environmental science, and in central to core technologies such as semiconductor fabrications, nanotechnology and plasma processing. In recent years the molecular physics also started significantly contributing to the area of the radiation damage at molecular level and thus cancer therapy improvement through both experimental and theoretical advances, developing new damage measurement and analysis techniques. It is therefore worth to summarise and highlight the most prominent findings from the AMP community that contribute towards better understanding of the fundamental processes in biologically-relevant systems as well as to comment on the experimental challenges that were met for more complex investigation targets.

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Proton-induced direct and indirect damage of plasmid DNA

Cited by 49 publications

References 44 publications

Validation of the radiobiology toolkit TOPAS-nBio in simple DNA geometries

Validation of the radiobiology toolkit TOPAS-nBio in simple DNA geometries

Improving proton therapy by metal-containing nanoparticles: nanoscale insights

Evaluating experimental molecular physics studies of radiation damage in DNA*

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