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Ionizing radiation causes chromosome aberrations, which are possible biomarkers to assess space radiation cancer risks. Using the Monte Carlo codes Relativistic Ion Tracks (RITRACKS) and Radiation-Induced Tracks, Chromosome Aberrations, Repair and Damage (RITCARD), we investigated how geometrical properties of the cell nucleus, irradiated with ion beams of linear energy transfer (LET) ranging from 0.22 keV/µm to 195 keV/µm, influence the yield of simple and complex exchanges. We focused on the effect of (1) nuclear volume by considering spherical nuclei of varying radii; (2) nuclear shape by considering ellipsoidal nuclei of varying thicknesses; (3) beam orientation; and (4) chromosome intermingling by constraining or not constraining chromosomes in non-overlapping domains. In general, small nuclear volumes yield a higher number of complex exchanges, as compared to larger nuclear volumes, and a higher number of simple exchanges for LET < 40 keV/µm. Nuclear flattening reduces complex exchanges for high-LET beams when irradiated along the flattened axis. The beam orientation also affects yields for ellipsoidal nuclei. Reducing chromosome intermingling decreases both simple and complex exchanges. Our results suggest that the beam orientation, the geometry of the cell nucleus, and the organization of the chromosomes within are important parameters for the formation of aberrations that must be considered to model and translate in vitro results to in vivo risks.
Assuntos
Aberrações Cromossômicas , Cromossomos , Núcleo Celular/genética , Núcleo Celular/efeitos da radiação , Cromossomos/genética , Humanos , Transferência Linear de Energia , Método de Monte CarloRESUMO
For missions beyond low Earth orbit to the moon or Mars, space explorers will encounter a complex radiation field composed of various ion species with a broad range of energies. Such missions pose significant radiation protection challenges that need to be solved in order to minimize exposures and associated health risks. An innovative galactic cosmic ray simulator (GCRsim) was recently developed at the NASA Space Radiation Laboratory (NSRL) at Brookhaven National Laboratory (BNL). The GCRsim technology is intended to represent major components of the space radiation environment in a ground analog laboratory setting where it can be used to improve understanding of biological risks and serve as a testbed for countermeasure development and validation. The current GCRsim consists of 33 energetic ion beams that collectively simulate the primary and secondary GCR field encountered by humans in space over the broad range of particle types, energies, and linear energy transfer (LET) of interest to health effects. A virtual workshop was held in December 2020 to assess the status of the NASA baseline GCRsim. Workshop attendees examined various aspects of simulator design, with a particular emphasis on beam selection strategies. Experimental results, modeling approaches, areas of consensus, and questions of concern were also discussed in detail. This report includes a summary of the GCRsim workshop and a description of the current status of the GCRsim. This information is important for future advancements and applications in space radiobiology.
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Radiação Cósmica , Proteção Radiológica , Voo Espacial , Estados Unidos , Humanos , United States National Aeronautics and Space Administration , Radiobiologia , CarmustinaRESUMO
Studying energy deposition by space radiation at the cellular scale provides insights on health risks to astronauts. Using the Monte Carlo track structure code RITRACKS, and the chromosome aberrations code RITCARD, we performed a modeling study of single-ion energy deposition spectra and chromosome aberrations for high-energy (>250 MeV/n) ion beams with linear energy transfer (LET) varying from 0.22 to 149.2 keV/µm. The calculations were performed using cells irradiated directly by mono-energetic ion beams, and by poly-energetic beams after particle transport in a digital mouse model, representing the radiation exposure of a cell in a tissue. To discriminate events from ion tracks directly traversing the nucleus, to events from δ-electrons emitted by distant ion tracks, we categorized ion contributions to microdosimetry or chromosome aberrations into direct and indirect contributions, respectively. The ions were either ions of the mono-energetic beam or secondary ions created in the digital mouse due to interaction of the beam with tissues. For microdosimetry, the indirect contribution is largely independent of the beam LET and minimally impacted by the beam interactions in mice. In contrast, the direct contribution is strongly dependent on the beam LET and shows increased probabilities of having low and high-energy deposition events when considering beam transport. Regarding chromosome aberrations, the indirect contribution induces a small number of simple exchanges, and a negligible number of complex exchanges. The direct contribution is responsible for most simple and complex exchanges. The complex exchanges are significantly increased for some low-LET ion beams when considering beam transport.
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The space radiation environment is qualitatively different from Earth, and its radiation hazard is generally quantified relative to photons using quality factors that allow assessment of biologically-effective dose. Two approaches exist for estimating radiation quality factors in complex low/intermediate-dose radiation environments: one is a fluence-based risk cross-section approach, which requires very detailed in silico characterization of the radiation field and biological cross sections, and thus cannot realistically be used for in situ monitoring. By contrast, the microdosimetric approach, using measured (or calculated) distributions of microdosimetric energy deposition together with empirical biological weighting functions, is conceptually and practically simpler. To demonstrate feasibility of the microdosimetric approach, we estimated a biological weighting function for one specific endpoint, heavy-ion-induced tumorigenesis in APC1638N/+ mice, which was unfolded from experimental results after a variety of heavy ion exposures together with corresponding calculated heavy ion microdosimetric energy deposition spectra. Separate biological weighting functions were unfolded for targeted and non-targeted effects, and these differed substantially. We folded these biological weighting functions with microdosimetric energy deposition spectra for different space radiation environments, and conclude that the microdosimetric approach is indeed practical and, in conjunction with in-situ measurements of microdosimetric spectra, can allow continuous readout of biologically-effective dose during space flight.
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To understand the biological effects of radiation, it is important to determine how ionizing radiation deposits energy in micrometric targets. The energy deposited in a target located in an irradiated tissue is a function of several factors such as the radiation type and the irradiated volume size. We simulated the energy deposited by energetic ions in spherical targets of 1, 2, 4, and 8 µm radii encompassed in irradiated parallelepiped volumes of various sizes using the stochastic radiation track structure code Relativistic Ion Tracks (RITRACKS). Because cells are usually part of a tissue when they are irradiated, electrons originating from radiation tracks in neighboring volumes also contribute to energy deposition in the target. To account for this contribution, we used periodic boundary conditions in the simulations. We found that the single-ion spectra of energy deposition in targets comprises two components: the direct ion hits to the targets, which is identical in all irradiation conditions, and the contribution of hits from electrons from neighboring volumes, which depends on the irradiated volume. We also calculated an analytical expression of the indirect hit contributions using the local effect model, which showed results similar to those obtained with RITRACKS.
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PURPOSE: For the past two decades, high-Z nanoparticles have been of high interest to improve the therapeutic outcomes of radiation therapy, especially for low-energy x-rays. Monte Carlo (MC) simulations have been used to evaluate the boost of dose deposition induced by Auger electrons near the nanoparticle surface, by calculating average energy deposition at the nanoscale. In this study, we propose to go beyond average quantities and quantify the stochastic nature of energy deposition at such a scale. We present results of probability density of the specific energy (restricted to ionization, excitation and electron attachment events) in cylindrical nanotargets of height and radius set at 10 nm. This quantity was evaluated for nanotargets located within 200 nm around 5-50 nm gold nanoparticles (GNPs), for 20-90 keV photon irradiation. METHODS: This nanodosimetry study was based on the MC simulation MDM that allows tracking of electrons down to thermalization energy. We introduced a new quantity, namely the probability enhancement ratio (PER), by estimating the probability of imparting to nanotargets a restricted specific energy larger than a threshold z 0 (1, 10, and 20 kGy), normalized to the probability for pure water. The PER was calculated as a function of the distance between the nanotarget and the GNP surface. The threshold values were chosen in light of the biophysical model NanOx that predicts cell survival by calculating local lethal events based on the restricted specific energy and an effective local lethal function. z 0 then represents a threshold above which the nanotarget damages induce efficiently cell death. RESULTS: Our calculations showed that the PER varied a lot with the GNP radius, the photon energy, z 0 and the distance of the GNP to the nanotarget. The highest PER was 95 when the nanotarget was located at 5 nm from the GNP surface, for a photon energy of 20 keV, a threshold of 20 kGy, and a GNP radius of 50 nm. This enhancement dramatically decreased with increasing GNP-nanotarget distances as it went below 1.5 for distances larger than 200 nm. CONCLUSIONS: The PER seems better adapted than the mean dose deposition to describe the formation of biological damages. The significant increase of the PER within 200 nm around the GNP suggests that severe damages could occur for biological nanotargets located near the GNP. These calculations will be used as an input of the biophysical model NanOx to convert PER into estimation of radiation-induced cell death enhanced by GNPs.
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Ouro , Nanopartículas Metálicas , Método de Monte Carlo , Fótons , ÁguaRESUMO
PURPOSE: To develop a particle transport code to compute w-values and stopping power of swift ions in liquid water and gases of interest for reference dosimetry in hadrontherapy. To analyze the relevance of inelastic and post-collisional processes considered. METHODS: The Monte Carlo code MDM was extended to the case of swift ion impact on liquid water (MDM-Ion). Relativistic corrections in the inelastic cross sections and the post-collisional Auger emission were considered. The effects of introducing different electronic excitation cross sections were also studied. RESULTS: The stopping power of swift ions on liquid water, calculated with MDM-Ion, are in excellent agreement with recommended data. The w-values show a strong dependence on the electronic excitation cross sections and on the Auger electron emission. Comparisons with other Monte Carlo codes show the relevance of both the processes considered and of the cross sections employed. W and w-values for swift electron, proton, and carbon ions calculated with the MDM and MDM-Ion codes are in very close agreement with each other and with the 20.8 eV experimental value. CONCLUSION: We found that w-values in liquid water are independent of ion charge and energy, as assumed in reference dosimetry for hadrontherapy from sparse experimental results for electron and ion impact on gases. Excitation cross sections and Auger emission included in Monte Carlo codes are critical in w-values calculations. The computation of this physical parameter should be used as a benchmark for micro-dosimetry investigations, to assess the reliability of the cross sections employed.
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Elétrons , Prótons , Íons , Método de Monte Carlo , Reprodutibilidade dos Testes , ÁguaRESUMO
Functionalized gold nanoparticles are investigated by density functional theory calculations in the context of cancer radiotherapy. Several typical experimental shapes, including nanostars, nanospheres, and nanorods, are modeled by optimizing Au clusters covered by organic monolayers composed of hydrated short-chain polyethylene glycol (PEG) ligands. The PEGylation stabilizes significantly the stellation of decahedral Au54 by deforming significantly its geometry at the spikes. The higher stability of the PEG molecules adsorbed on this stellated nanocluster with respect to the more spherical icosahedral Au55 and truncated octahedral Au79 leads to a larger energy cost to desorb them and thus a weaker propensity for the starred nanoparticle to exchange ligands with the cell membrane, in agreement with experiments. These results open interesting possibilities for advancing our understanding of the cellular uptake of gold nanoparticles.
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Nanopartículas Metálicas/química , Polietilenoglicóis/química , Adsorção , Teoria da Densidade Funcional , Ouro/química , Ligantes , Modelos Químicos , Nanosferas/química , Nanotubos/químicaRESUMO
Solvated gold nanoparticles have been modeled in the fluxional regime by density functional theory including dispersion forces for an extensive set of conventional morphologies. The study of isolated adsorption of one water molecule shows that the most stable adsorption forms are similar (corners and edges) regardless of the nanoparticle shape and size, although the adsorption strength differs significantly (0.15 eV). When a complete and explicit water solvation shell interacts with gold nanoclusters, metastable in vacuum and presenting a predominance of (100) square facets (ino-decahedra Au55 and Au147), these nanoparticles are found unstable and transform into the closest morphologies exhibiting mainly (111) triangular facets and symmetries. The corresponding adsorption strength per water molecule becomes independent of shape and size and is enhanced by the formation of two hydrogen bonds on average. For applications in radiotherapy, this study suggests that the shapes of small gold nanoparticles should be homogenized by interacting with the biological environment.