Simulation of DNA fragment distributions after irradiation with photons

Friedland, W.; Jacob, Peter; Paretzke, H. G.; Merzagora, M.; Ottolenghi, A.

doi:10.1007/s004110050136

Cited by 140 publications

(116 citation statements)

References 19 publications

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“…In particular, the coupling of the track-structure modules with a detailed model of the DNA molecule (including higher-order chroma- tin organization levels), previously applied to DNA fragmentation studies [3,4] will make it possible to follow the propagation of the uncertainties related to the physical and chemical stages down to observable biological end-points.…”

Section: Discussionmentioning

confidence: 99%

“…This code also provides a detailed (atom-by-atom) description of the DNA and chromatin structures, thus making it possible to test working hypotheses on the radiation action mechanisms in a quantitative way and to perform extrapolations safer than hitherto possible to parameter regions where no experimental data exist (e.g., to low doses). In previous work [2,3,4], PARTRAC has been used to model the spectra of various types of DNA damage induced by different radiation fields. In this work, an explicit description of the production, diffusion and interaction of water radicals and molecular products was included in the code, with the main aim to quantify the role of the uncertainties in the parameters controlling liquid water radiolysis.…”

Section: Introductionmentioning

confidence: 99%

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Stochastic aspects and uncertainties in the prechemical and chemical stages of electron tracks in liquid water: a quantitative analysis based on Monte Carlo simulations

Ballarini¹,

Biaggi²,

Merzagora³

et al. 2000

Radiation and Environmental Biophysics

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A new physical module for the biophysical simulation code PARTRAC has recently been developed, based on newly derived electron inelastic-scattering cross-sections in liquid water. In the present work, two modules of PARTRAC describing the production, diffusion and interaction of chemical species were developed with the specific purpose of quantifying the role of the uncertainties in the parameters controlling the early stages of liquid water radiolysis. A set of values for such parameters was identified, and time-dependent yields and frequency distributions of chemical species produced by electrons of different energies were calculated. The calculated yields were in good agreement with available data and simulations, thus confirming the reliability of the code. As the primary-electron energy decreases down to 1 keV, the *OH decay kinetics were found to get faster, reflecting variations in the spatial distribution of the initial energy depositions. In agreement with analogous works, an opposite trend was found for energies of a few hundred eV, due to the very small number of species involved. The spreading effects shown at long times by *OH frequency distributions following 1 keV irradiation were found to be essentially due to stochastic aspects of the chemical stage, whereas for 1 MeV tracks the physical and pre-chemical stages also were found to play a significant role. Relevant differences in the calculated e(aq) -yields were found by coupling the physics of PARTRAC with descriptions of the pre-chemical and chemical stages adopted in different models. This indicates a strict interrelation of the various stages, and thus a strong dependence of the parameter values on the assumptions made for the preceding and subsequent stages of the process. Although equally acceptable results can be obtained starting from different assumptions, it is necessary to keep control of such uncertainties, since they can significantly influence the modeling of radical attack on DNA and, more generally, radiobiological damage estimation. This study confirms the need for new, independently derived data on specific steps of water radiolysis, to be included in comprehensive biophysical simulation codes.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Stochastic aspects and uncertainties in the prechemical and chemical stages of electron tracks in liquid water: a quantitative analysis based on Monte Carlo simulations

Ballarini¹,

Biaggi²,

Merzagora³

et al. 2000

Radiation and Environmental Biophysics

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“…(15,64) Modern models of chromatin structure (46,65) can be integrated with simple models of DSB motion and misrejoining as well as with previously developed, sophisticated radiation track codes describing physical and radiochemical aspects of radiation. (14,17,66,67) Such aberration modeling is probabilistic, implemented by what are called Monte Carlo techniques, where the computer in effect ''rolls dice'' to give extremely detailed output. The time course of aberration formation is simulated in each cell.…”

Section: Modeling Aberration Formation Mechanisms Quantitativelymentioning

confidence: 99%

Radiation‐induced chromosome aberrations: Insights gained from biophysical modeling

et al. 2002

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Enzymatic misrepair of ionizing-radiation-induced DNA damage can produce large-scale rearrangements of the genome, such as translocations and dicentrics. These and other chromosome exchange aberrations can cause major phenotypic alterations, including cell death, mutation and neoplasia. Exchange formation requires that two (or more) genomic loci come together spatially. Consequently, the surprisingly rich aberration spectra uncovered by recently developed techniques, when combined with biophysically based computer modeling, help characterize large-scale chromatin architecture in the interphase nucleus. Most results are consistent with a picture whereby chromosomes are mainly confined to territories, chromatin motion is limited, and interchromosomal interactions involve mainly territory surfaces. Aberration spectra and modeling also help characterize DNA repair/misrepair mechanisms. Quantitative results for mammalian cells are best described by a breakage-and-reunion model, suggesting that the dominant recombinational mechanism during the G(0)/G(1) phase of the cell cycle is non-homologous end-joining of radiogenic DNA double strand breaks. In turn, better mechanistic and quantitative understanding of aberration formation gives new insights into health-related applications.

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“…It is known that megavoltage radiation (X/γ-rays, α-particles, and heavy ions) ionizes the water molecule and creates neutral free-radicals and aqueous electrons [1][2][3][4][5][6][7][8][9] . In particular OH-radicals with a very short life-time that is reported to be within nano-seconds 10 , are major contributors to the single/double strand breaking of the DNA molecules and the nucleotide-base damage, as 2/3 of environment surrounding DNA molecules in the cell-nucleus is composed of water molecules 4 .…”

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confidence: 99%

Reactive Molecular Dynamics Study on the First Steps of DNA Damage by Free Hydroxyl Radicals

2011

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We employ a large scale molecular simulation based on bond-order ReaxFF to simulate the chemical reaction and study the damage to a large fragment of DNA-molecule in the solution by ionizing radiation. We illustrate that the randomly distributed clusters of diatomic OH-radicals that are primary products of megavoltage ionizing radiation in water-based systems are the main source of hydrogen-abstraction as well as formation of carbonyl-and hydroxyl-groups in the sugar-moiety that create holes in the sugar-rings. These holes grow up slowly between DNA-bases and DNA-backbone and the damage collectively propagate to DNA single and double strand break.PACS numbers: 87.64.Aa It is known that megavoltage radiation (X/γ-rays, α-particles, and heavy ions) ionizes the water molecule and creates neutral free-radicals and aqueous electrons 1-9 . In particular OH-radicals with a very short life-time that is reported to be within nano-seconds 10 , are major contributors to the single/double strand breaking of the DNA molecules and the nucleotide-base damage, as 2/3 of environment surrounding DNA molecules in the cell-nucleus is composed of water molecules 4 . Various effects of the ionizing radiation on biological systems that ranges from the development of genetic aberrations, carcinogenesis to aging, have attributed to the role of free radicals.Computational modeling is a valuable tool in understanding the basic mechanisms that underlie DNA damage. Great effort has been devoted to the statistical modeling of the damage sites based on Monte-Carlo (MC) sampling, using empirical reaction rates and radiation scattering cross-sections 4-9 . These models are limited to MC sampling on a static structure of DNA or dynamical models based on molecular-mechanics (MM) and empirical force-fields (FF), e.g. AMBER/CHARMM FF, that are developed for simulation of the non-reactive aspects of bio-molecules.The reactive aspects and the time evolution of the multi-site DNA damages driven by cascade of chemical reactions, that are beyond MM methods and empirical FF, require the calculation of the potential energies onthe-fly using first-principle quantum mechanical (QM) models. Recently ab-initio simulations of the hydrogen abstraction were developed 11-15 . However realistic modeling of DNA molecule with its environment requires extensive computer resources and is a major draw-back of QM methods. The DFT calculation for hydrogen abstraction in vacuum is limited to the initial damage of a single base [11][12][13] or single sugar-moiety 15 . Despite recent advances in QM/MM methods that allows simulation of larger molecules 14 and inclusion of solvation 15 , the real time simulation of DNA-damage remains still elusive.To address the above considerations regarding to the large scale modeling of DNA-damage, we have studied the evolution of randomly distributed hydroxyl-radicals in small pockets surrounding the DNA-molecule at room temperature using molecular dynamics simulations where the atomic interactions are described by the reactive force f...

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Simulation of DNA fragment distributions after irradiation with photons

Cited by 140 publications

References 19 publications

Stochastic aspects and uncertainties in the prechemical and chemical stages of electron tracks in liquid water: a quantitative analysis based on Monte Carlo simulations

Stochastic aspects and uncertainties in the prechemical and chemical stages of electron tracks in liquid water: a quantitative analysis based on Monte Carlo simulations

Radiation‐induced chromosome aberrations: Insights gained from biophysical modeling

Reactive Molecular Dynamics Study on the First Steps of DNA Damage by Free Hydroxyl Radicals

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