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Braselmann H Kulka U Baumgartner A Eder C Müller I Figel M Zitzelsberger H 《Mutation research》2005,578(1-2):124-133
For a retrospective dose estimation of human exposure to ionising radiation, a partial genome analysis is routinely used to quantify radiation-induced chromosome aberrations. For this purpose, fluorescence in situ hybridisation (FISH) with whole chromosome painting probes for selected chromosomes is usually applied covering about 20% of the whole genome. Since genome-wide screening techniques like spectral karyotyping (SKY) and multiplex FISH (mFISH) have been developed the detection of radiation-induced aberrations within the whole genome has now become feasible. To determine the correspondence between partial and whole genome analysis of radiation-induced chromosome aberrations, they were measured comprehensively in this study using in vitro irradiated blood samples from three donors. We were able to demonstrate that comparable results can be detected with both approaches. However, complex aberrations might be misinterpreted by partial genome analysis. We therefore conclude that whole genome analysis by SKY is useful especially in the high dose range to correct aberration data for complex exchange aberrations. 相似文献
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Andreev SG Eĭdel'man IuA Talyzina TA 《Radiatsionnaia biologiia, radioecologiia / Rossi?skaia akademiia nauk》2006,46(1):16-19
The quantitative prediction of the biological effects of radiation is one of the actual tasks of radiobiology. The experimental study may be impossible under certain conditions (low doses, complex radiation fields, etc). The development of theoretical tools is required to predict biological and medical consequence of the irradiation of cell and organism. The effect under the consideration in the present paper is chromosome aberrations (CA) induced by low and high LET radiation. One of the most uncertain factors in CA prediction is the impact of chromosomal and nuclear architecture. In the present study the quantitative evaluation of the mechanisms of CA induction are discussed in the framework of the biophysical modelling technique taking into account interphase chromosomes structure in the nucleus of living (human) cell. We show that the surface contacts mechanism of interchromosomal aberrations (interchange) formation does not explain the observed ratio of simple/complex interchanges induced by both low and high LET radiation. The chromatin structure repositioning following irradiation is proposed as a possible mechanism involved in the formation of the complex aberrations. 相似文献
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We present a computational model for calculating the yield of radiation-induced chromosomal aberrations in human cells based on a stochastic Monte Carlo approach and calibrated using the relative frequencies and distributions of chromosomal aberrations reported in the literature. A previously developed DNA-fragmentation model for high- and low-LET radiation called the NASARadiationTrackImage model was enhanced to simulate a stochastic process of the formation of chromosomal aberrations from DNA fragments. The current version of the model gives predictions of the yields and sizes of translocations, dicentrics, rings, and more complex-type aberrations formed in the G(0)/G(1) cell cycle phase during the first cell division after irradiation. As the model can predict smaller-sized deletions and rings (<3 Mbp) that are below the resolution limits of current cytogenetic analysis techniques, we present predictions of hypothesized small deletions that may be produced as a byproduct of properly repaired DNA double-strand breaks (DSB) by nonhomologous end-joining. Additionally, the model was used to scale chromosomal exchanges in two or three chromosomes that were obtained from whole-chromosome FISH painting analysis techniques to whole-genome equivalent values. 相似文献
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Misrejoining of DNA double-strand breaks (DSBs) was measured in human primary fibroblasts after exposure to X rays and high-LET particles (helium, nitrogen and iron) in the dose range 10-80 Gy. To measure joining of wrong DNA ends, the integrity of a 3.2-Mbp restriction fragment was analyzed directly after exposure and after 16 h of repair incubation. It was found that the misrejoining frequency for X rays was nonlinearly related to dose, with less probability of misrejoining at low doses than at high doses. The dose dependence for the high-LET particles, on the other hand, was closer to being linear, with misrejoining frequencies higher than for X rays, particularly at the lower doses. These experimental results were simulated with a Monte Carlo approach that includes a cell nucleus model with all 46 chromosomes present, combined with realistic track structure simulations to calculate the geometrical positions of all DSBs induced for each dose. The model assumes that the main determinant for misrejoining probability is the distance between two simultaneously present DSBs. With a Gaussian interaction probability function with distance, it was found that the data for both low- and high-LET radiation could be fitted with an interaction distance (sigma of the Gaussian curve) of 0.25 microm. This is half the distance previously found to best fit chromosomal aberration data in human lymphocytes using the same methods (Holley et al., Radiat. Res. 158, 568-580, 2002). The discrepancy may indicate inadequacies in the chromosome model, for example insufficient chromosomal overlap, but may also be partly due to differences between fibroblasts and lymphocytes. 相似文献
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Apoptosis induced by high- and low-LET radiations 总被引:2,自引:0,他引:2
Cell death after irradiation occurs by apoptosis in certain cell populations in tissues. The phenomenon also occurs after high linear energy transfer (LET) irradiation, and the relative biological effectiveness (RBE) is 3 to 4 (with respect to low-LET radiation and apoptosis in intestinal crypts) for neutrons with energies of 14 MeV and up to 600 MeV. It is thought thatp53 plays a role in the phenomenon, as radiation-induced apoptosis is not observed inp53-null animals. 相似文献
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Species comparisons concerning radiation-induced dominant lethals and chromosome aberrations 总被引:1,自引:0,他引:1
After X-irradiation of post-meiotic stages, male mice, guinea-pigs, rabbits and golden hamsters differed both in general sensitivity to the induction of dominant lethals, and in the relative sensitivity of the various spermatogenic stages. Guinea-pigs were the least sensitive, and hamsters had a different stage sensitivity pattern, with mature sperm the most sensitive stage. 相似文献
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Studies on some radiation-induced chromosome aberrations in man 总被引:1,自引:0,他引:1
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Structural analysis of heavy ion radiation-induced chromosome aberrations by atomic force microscopy 总被引:9,自引:0,他引:9
Murakami M Minamihisamatsu M Sato K Hayata I 《Journal of biochemical and biophysical methods》2001,48(3):293-301
Heavy ion radiation (high linear energy transfer, LET, radiation) induces various types of chromosome aberration. In this report, we describe a new method employing an atomic force microscope (AFM) for nanometer-level structural analysis of chromosome damage induced by heavy ion irradiation. Metaphase mouse chromosomes with chromatid gap or chromatid breaks induced by heavy ion irradiation were marked under a light microscope. Then the detailed structure of chromosomes of Giemsa-stained or unstained samples was visualized by the AFM. The height data of chromosomes obtained by AFM provided useful information to distinguish chromatid gaps and breaks. A fibrous structure was observed on the unstained chromosome, the average width of which was about 45.8 nm in the image of AFM. These structures were considered to be 30-nm fibers on the chromosome. The structure of the break point regions induced by neon- or carbon-ion irradiation was imaged by AFM. In some cases, the fibrous structure of break points was detected by AFM imaging after carbon ion irradiation. These observations indicated that AFM is a useful tool for analysis of chromosome aberrations induced by heavy ion radiation. 相似文献
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A quantitative computer model was applied to simulate the three-dimensional (3D) spatial organization of chromatin in human cell nuclei under defined conditions of virtual irradiation to explore the implications of spatial organization on chromosome aberrations. To calibrate the virtual irradiation algorithm, a dose-dependent spectrum of radiation-induced chromosome aberrations such as dicentrics, translocations and centric rings was calculated for low-LET radiation doses ranging from 0.5 to 5 Gy. This was compared with the results from experimental studies. While the dose-response curves calculated from model simulations agree well with experimental dose-response curves for dicentrics and translocations, centric rings are significantly more frequent in the model simulation than in experiments despite taking into account exclusive arm territories in the applied Spherical 1 Mbp Chromatin Domain (SCD) computer model explicitly. Taking into account the non-random positioning of chromosome territories observed in lymphocyte cell nuclei (a so-called gene density-correlated arrangement of chromosome territories), aberration frequencies were calculated with the calibrated irradiation algorithm to investigate the impact of chromosome territory neighborhood effects (proximity effects). The absolute frequencies of pairwise exchanges agree well with those found in an experimental study. In conclusion, the results obtained using the computer model approach presented here based on only a few adjustable parameters correlated well with those of experimental studies of chromosome aberration frequencies. Thus the model may be a useful tool in radiation-induced cancer risk estimates in combination with epidemiological studies. 相似文献
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Whole-blood leukocyte cultures were evaluated at intervals up to 20 weeks following the exposure of mature pigs to 150 or 200 R whole-body doses of γ-radiation. Lymphocyte number was depressed to approximately 35% of preirradiation values by 48 h postexposure; chromosome aberration levels also quite drastically during this period. A rapid decrease in aberrations per cell indicated selective removal of cells containing chromosome anomalues during the early postirradiation period. Elevated levels of both one-track and two-track aberrations persisted at 20 weeks although the former had been at preirradiation levels at 12 and 16 weeks. 相似文献
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Chudoba I Hickmann G Friedrich T Jauch A Kozlowski P Senger G 《Cytogenetic and genome research》2004,104(1-4):390-393
Precise breakpoint definition of chromosomal rearrangements using conventional banding techniques often fails, especially when more than two breakpoints are involved. The classic banding procedure results in a pattern of alternating light and dark bands. Hence, in banded chromosomes a specific chromosomal band is rather identified by the surrounding banding pattern than by its own specific morphology. In chromosomal rearrangements the original pattern is altered and therefore the unequivocal determination of breakpoints is not obvious. The multicolor banding technique (mBAND, see Chudoba et al., 1999) is able to identify breakpoints unambiguously, even in highly complex chromosomal aberrations. The mBAND technique is presented and illustrated in a case of intrachromosomal rearrangement with seven breakpoints all having occurred on one chromosome 16, emphasizing the unique analyzing power of mBAND as compared to conventional banding techniques. 相似文献
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Cigarrán S Barrios L Caballín MR Barquinero JF 《Cytogenetic and genome research》2004,104(1-4):168-172
The purpose of the present work was to determine if the described reduction in the frequency of radiation-induced chromosome aberrations by DMSO is homogeneous within different human chromosomes. Blood samples were irradiated with 4 Gy of X-rays in absence and presence of 0.5 M DMSO. FISH painting was carried out independently for human chromosomes 1, 2, 3, 4, 7, 11 and 12. The observed frequencies of apparently simple translocations and dicentrics for all these chromosomes, showed a homogeneous reduction when the irradiation was done in the presence of DMSO. Moreover, a better fit between the observed and expected frequencies was obtained when (DNA content)2/3 was used to calculate the expected frequencies, instead of just the DNA content. This result supports the idea that for exchange type aberrations, a better adjustment is obtained when the surface area of spherical chromosome territories is considered. 相似文献
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In interphase, chromosomes occupy defined nuclear volumes known as chromosome territories. To probe the biological consequences of the described nonrandom spatial positioning of chromosome territories in human lymphocytes, we performed an extensive FISH-based analysis of ionizing radiation-induced interchanges involving chromosomes 1, 4, 18 and 19. Since the probability of exchange formation depends strongly on the spatial distance between the damage sites in the genome, a preferential formation of exchanges between proximally positioned chromosomes is expected. Here we show that the spectrum of interchanges deviates significantly from one expected based on random chromosome positioning. Moreover, the observed exchange interactions between specific chromosome pairs as well as the interactions between homologous chromosomes are consistent with the proposed gene density-related radial distribution of chromosome territories. The differences between expected and observed exchange frequencies are more pronounced after exposure to densely ionizing neutrons than after exposure to sparsely ionizing X rays. These experiments demonstrate that the spatial positioning of interphase chromosomes affects the spectrum of chromosome rearrangements. 相似文献
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Anderson RM Papworth DG Stevens DL Sumption ND Goodhead DT 《Cytogenetic and genome research》2006,112(1-2):35-44
Complex chromosome aberrations (any exchange involving three or more breaks in two or more chromosomes) are effectively induced in peripheral blood lymphocytes (PBL) after exposure to low doses (mostly single particles) of densely ionising high-linear energy transfer (LET) alpha-particle radiation. The complexity, when observed by multiplex fluorescence in situ hybridisation (m-FISH), shows that commonly four but up to eight different chromosomes can be involved in each rearrangement. Given the territorial organisation of chromosomes in interphase and that only a very small fraction of the nucleus is irradiated by each alpha-particle traversal, the aim of this study is to address how aberrations of such complexity can be formed. To do this, we applied theoretical "cycle" analyses using m-FISH paint detail of PBL in their first cell division after exposure to high-LET alpha-particles. In brief, "cycle" analysis deconstructs the aberration "observed" by m-FISH to make predictions as to how it could have been formed in interphase. We propose from this that individual high-LET alpha-particle-induced complex aberrations may be formed by the misrepair of damaged chromatin in single physical "sites" within the nucleus, where each "site" is consistent with an "area" corresponding to the interface of two to three different chromosome territories. Limited migration of damaged chromatin is "allowed" within this "area". Complex aberrations of increased size, reflecting the path of alpha-particle nuclear intersection, are formed through the sequential linking of these individual sites by the involvement of common chromosomes. 相似文献