共查询到20条相似文献,搜索用时 15 毫秒
1.
Stísová V Goffinont S Spotheim-Maurizot M Davídková M 《Radiation protection dosimetry》2006,122(1-4):106-109
The exposure of a DNA-protein regulatory complex to ionising radiation induces damage to both partner biomolecules and thus can affect its functioning. Our study focuses on a complex formed by the estrogen response element (ERE) DNA and the recombinant human estrogen receptor alpha (ER), which mediates the signalling of female sex hormones, estrogens. The method of native polyacrylamide retardation gel electrophoresis is used to study the stability of the complex under irradiation by low LET radiation ((60)Co gamma rays) and the ability of the separately irradiated partners to form complexes. The relative probabilities of ERE DNA strand breakage and base damages as well as the probabilities of damages to the ER binding domain are calculated using the Monte Carlo method-based model RADACK. 相似文献
2.
B M Sutherland P V Bennett M Saparbaev J C Sutherland J Laval 《Radiation protection dosimetry》2001,97(1):33-38
Clustered DNA damages--two or more lesions (oxidised bases. abasic sites, or strand breaks) within a few DNA helical turns on opposing strands--are induced in DNA in solution and in vivo in human cells by ionising radiation. They have been postulated to be difficult to repair, and thus of potentially high biological significance. Since the total of clustered damages produced by ionising radiation is at about 3 to 4 times higher levels than double-strand breaks and are apparently absent in unirradiated cells, levels of clustered damages present immediately alter radiation exposure could serve as sensitive dosemeters of radiation exposure. Since some clusters may not be repairable and may accumulate in cells, they might also be useful as integrating dosemeters of biological effects of radiation damage. 相似文献
3.
Energy from low LET ionising radiation, such as X rays and gamma rays, is deposited in the water surrounding the DNA molecule such that between 2 to 5 radical pairs are generated within a radius of I to 4 nm. As a result, multiple single lesions, including oxidised purine or pyrimidine bases, sites of base loss, and single-strand breaks, can be formed in DNA from the same radiation energy deposition event. The single lesions in these so-called multiply damaged sites or clustered lesions are repaired by base excision repair. Here we show that clustered DNA damages are formed in bacterial cells by ionising radiation and are converted to lethal double-strand breaks during attempted repair. In wild type cells possessing the oxidative DNA glycosylases that recognise and cleave DNA at repairable single damages, double-strand breaks are formed at radiation-induced clusters during post-irradiation incubation and in a dose-dependent fashion. Mutant cells lacking these enzymes do not form double-strand breaks post-irradiation and are substantially more radioresistant than wild type cells. These radioresistant mutant cells can be made radiosensitive by overexpressing one of the oxidative DNA glycosylases. Thus the effect of the oxidative DNA glycosylases in potentiating DNA damage must be considered when estimating radiation risk. 相似文献
4.
Tabocchini MA Belli M Campa A Löbrich M Sapora O Simone G Stenerlöw B 《Radiation protection dosimetry》2002,99(1-4):123-128
Use of cellular systems capable of undergoing in vitro differentiation can give useful information on the basic mechanisms of cellular radiation sensitivity. During differentiation the cellular organisation, including the nuclear structure and the intracellular concentration of several compounds and enzymes change drastically. Accordingly, radiation response to ionising radiation is also expected to change. The human proerythroblastoid cell line K562 can be induced to pseudoerythroid differentiation. This process has been characterised and studies have been carried out on DNA single strand break and double strand break induction and repair before and after differentiation commitment. Rejoining studies have been performed for both types of damage and correct double strand break rejoining has been also measured in particular genomic locations. An overview is presented of these results together with preliminary data recently obtained on radiation induced DNA fragmentation as a function of radiation quality. 相似文献
5.
The overall cellular damage induced by ionising radiation is determined by the number and spatial distribution of initial ionisations and excitations within the critical volume. This paper focuses on the physical and chemical phase of the radiation action chain following the decay of DNA-bound 123I and 125I. Monte Carlo simulations of these nuclides' decay provide electron emission spectra which are used as input data for track structure calculations. In combination with DNA models, these calculations allow the specific radiation source to be characterised in terms of DNA strand break patterns. The distribution of these patterns indicates that 125I produces much more severe breaks than 123I. The ratio of complex DSBs induced by both iodine isotopes correlates with the differences in cell killing effectiveness reported from in vitro survival experiments. 相似文献
6.
Ionising radiation induces a variety of chemical modifications to DNA, ranging from simple, isolated lesions to clustered DNA damage, in which two or more lesions are formed within a few tens of base pairs by a single radiation track. Multiple lesions, e.g. tandem lesions and amplification of damage, may also be induced in DNA by reaction with a single hydroxyl radical. It has been proposed from biophysical modelling that clustered DNA damage is less repairable and therefore contributes to the biological severity of ionising radiation. In this review, some evidence is presented which indicates that non-double strand break (non-DSB) clustered DNA damage is induced in significant yield, relative to that of DSBs, in mammalian cells. Enzymatic processing of clustered DNA damage in synthetic oligonucleotides has been shown to be compromised, depending on the nature of the lesions present. The role of clustered DNA damage in the early stages of the development of radiation-induced carcinogenesis remains to be addressed. 相似文献
7.
8.
Sanche L 《Radiation protection dosimetry》2002,99(1-4):57-62
It has recently been shown that 3-20 eV electron impact on vacuum-dry samples of plasmid DNA induced substantial yields of single and double strand breaks (SSBs and DSBs). These results are summarised in the present article along with those obtained from the fragmentation of elementary components (i.e. condensed H2O, bases and sugar analogues) of DNA induced by low energy electron impact under ultra high vacuum conditions. By comparing the results from these experiments, it is possible to determine fundamental mechanisms by which low energy electrons damage DNA. The decay of transient anions formed on the DNA's basic components is found to play a crucial role in producing SSBs and DSBs. Since a large portion of the energy deposited by ionising radiation first leads to the production of low energy secondary electrons, these findings provide basic knowledge necessary to understand the genotoxic effects of high energy radiation and eventually modify these effects at the molecular level. 相似文献
9.
Watanabe R Wada S Funayama T Kobayashi Y Saito K Furusawa Y 《Radiation protection dosimetry》2011,143(2-4):186-190
Radial energy deposition distribution, the distribution of DNA strand breaks and their yields were simulated by Monte Carlo track structure simulation for C and Ne ions with the same linear energy transfer (LET) around 450 keV/μm. The radial DNA damage distribution shows different pattern for C and Ne ions. Double strand break (DSB) are mostly formed in the central area, while the single strand break (SSB) tends to spread to the surrounding area. It is also shown that the production efficiency of the SSB and DSB depends on the radial distance. This result shows reasonable agreement with the recently obtained experimental observation, which indicates that different types of DNA damage shows different distribution patterns around C and Ne ion paths in cell nuclei. 相似文献
10.
The amazing feature of ionising radiation (IR) as a DNA damaging agent is the range of lesions it induces. Such lesions include base damage, single strand breaks (SSBs), double strand breaks (DSBs) of varying complexity and DNA cross links. A range of DNA damage response mechanisms operate to help maintain genomic stability in the face of such damage. Such mechanisms include pathways of DNA repair and signal transduction mechanisms. Increasing evidence suggests that these pathways operate co-operatively. In addition, the relative impact of one mechanism over another most probably depends upon the cell cycle phase and tissue type. Here, the distinct damage response pathways are reviewed and the current understanding of the interplay between them is considered. Since DNA DSBs are the major lethal lesion induced by IR, the focus lies in the mechanisms responding to direct or indirectly induced DSBs. 相似文献
11.
Stenerlöw B Höglund E Elmroth K Karlsson KH Radulescu I 《Radiation protection dosimetry》2002,99(1-4):137-141
Analysis of DNA fragmentation and repair in relation to radiation quality may give important information about the role of break complexity and correlated double strand breaks (DSBs). DNA fragment analysis was performed by pulsed-field gel electrophoresis after exposure to different radiation qualities. Normal human fibroblasts were irradiated with boron ions (40, 80 and 160 keV.micron-1), nitrogen ions (80, 125, 175 and 225 keV.micron-1) and neon ions (225 and 300 keV.micron-1). The amount of DNA less than 1.1 Mbp decreased with increasing linear energy transfer (LET) for all three ions. When theoretical random distributions were subtracted from the experimental data for 225 keV.micron-1 nitrogen ions in all size intervals (5-5700 kbp), there was a significant non-random distribution of DSBs for sizes up to 1-3 Mbp. This non-random distribution of breaks, probably produced by intra-track correlated DSBs, may constitute a substantial portion of the high-LET induced DSBs. 相似文献
12.
Rasolonjatovo AH Shiomi T Nakamura T Nishizawa H Tsudaka Y Fujiwara H Araki H Matsuo K 《Radiation protection dosimetry》2002,99(1-4):77-80
Modelling and calculations are presented for the spectrum of initial DNA damage produced by 100 eV to 100 keV energetic electrons. Analysis of the initial spectrum of damage, based upon the source (direct energy deposition and reactions with diffusing OH radicals) and complexity of damage, indicates that the majority of the interactions cause no damage to DNA and any damage that does occur is most likely to be a simple single strand break (SSB). The fraction of complex damage for energetic electrons is lower than that induced by low energy electrons and ultrasoft X rays but still represents an appreciable fraction (20-30%) of the total double strand breaks (DSBs). Relative yields of strand breaks are investigated for dependence on the assumed energy deposition threshold and on the probability of the hydroxyl radicals to produce a single strand break. The ratio of direct to indirect damage does not change significantly across the electron energy range investigated and the values lie well within the experimental data. The direct energy deposition in DNA represents a larger proportion of the damage although the contribution from the hydroxyl radicals is also substantial, both in terms of the absolute yield of the breaks and the complexity of the damage. 相似文献
13.
Although DNA damage is widely viewed as a critical target for the induction of cell killing by ionising radiation, the exact nature of DNA damage responsible for these effects is unknown. To address this issue, the probability of forming lethal damage by single proton tracks, derived from published survival data for Chinese hamster V79 cells irradiated by protons with energies from 0.57 to 5.01 MeV, has been compared to estimated yields of clustered DNA lesions and repair outcomes calculated with Monte Carlo models. The reported studies provide new information about the potential relationship between the induction and repair of clustered DNA damage and trends in the expected number of lethal events for protons with increasing linear energy transfer (LET). A good correlation was found between the number of lethal events in V79 cells and the induction of double-strand breaks (DSBs) consisting of three or more elementary DNA lesions. For the yields of other types of DNA damage, as well as point mutations formed through the misrepair of base damage and single-strand breaks, observed trends with increasing LET are not consistent with trends in the yields of lethal events. This observation suggests that the relative biological effectiveness (RBE) of protons of varying quality may be more closely related to the induction of complex DSBs rather than other forms of damage. 相似文献
14.
The generalised state-vector model of radiation carcinogenesis (SVM) simulates radiation induced biological effects by expressing the transition rates between the various initiation and promotion stages in terms of dose rate for low and high linear energy transfer (LET) particles. In the present work, the SVM has been reformulated to incorporate single track characteristics of particles with varying LET. Transition rates of the initiation phase were expressed as functions of LET by describing the complexity and clustering of DNA double strand breaks (DSBs) and its effect on repair kinetics, while the promotion phase was reformulated based on a multi-target single-hit hypothesis. Such an approach allows the consideration of hit frequencies and the variability of the specific energy and LET spectra of radon progeny alpha particles in bronchial target cells for different exposure conditions. 相似文献
15.
Urushibara A Shikazono N Watanabe R Fujii K O'Neill P Yokoya A 《Radiation protection dosimetry》2006,122(1-4):163-165
We present here evidence showing that the yields of DNA lesions induced by He(2+) ions strongly depend on Linear energy transfer (LET). In this study, hydrated plasmid DNA was irradiated with He(2+) ions with LET values of 19, 63 and 95 keVmicrom(-1). The yields of prompt single-strand breaks (SSBs) are very similar at the varying LET values, whereas the yields of prompt double-strand breaks (DSBs) increase with increasing LET. Further, base lesions were revealed as additional strand breaks by post-irradiation treatment of the DNA with endonuclease III (Nth) and formamidopyrimidine-DNA glycosylase (Fpg). The reduction in the yield of these enzymatically induced SSBs and DSBs becomes significant as the LET increases. These results suggest that the clustering of DNA lesions becomes more probable in regions of high LET. 相似文献
16.
When a charged-particle track intercepts the chromatin fibre in DNA of mammalian cells, clustered damage is induced depending on the DNA conformation, local environment and track structure. Intra-track correlated DNA damage may have a higher probability of being mis-repaired or left un-repaired. Fragment size-distributions of DNA double strand breaks (DSBs) induced in primary human fibroblasts by 240 kVp X rays and 238Pu alpha particles (110 keV.micron-1) were resolved using pulsed-field gel electrophoresis (PFGE). By monitoring DSB rejoining kinetics and changes in the fragment size distribution with repair time, the relevance of spatial association of DSBs in determining rejoining kinetics was investigated. Rejoining kinetics appeared bi-phasic and independent of the size of the DNA fragments for both radiation qualities, with high LET radiation-induced DSBs repairing more slowly. Results suggest that local complexity of individual DSBs, rather than spatial association with other breaks is more significant in the determination of rejoining kinetics. 相似文献
17.
Esposito G Belli M Campa A Cherubini R Cuttone G Dini V Furusawa Y Gerardi S Simone G Sorrentino E Tabocchini MA 《Radiation protection dosimetry》2006,122(1-4):166-168
Experimental data on DNA double strand break (DSB) induction in human fibroblasts (AG1522), following irradiation with several radiation qualities, namely gamma rays, 0.84 MeV protons, 58.9 MeV u(-1) carbon ions, iron ions of 115 MeV u(-1), 414 MeV u(-1), 1 GeV u(-1), and 5 GeV u(-1), are presented. DSB yields were measured by calibrated Pulsed Field Gel Electrophoresis in the DNA fragment size range 0.023-5.7 Mbp. The DSB yields show little LET dependence, in spite of the large variation of the latter among the beams, and are slightly higher than that obtained using gamma rays. The highest yield was found for the 5 GeV u(-1) iron beam, that gave a value 30% higher than the 1 GeV u(-1) iron beam. A phenomenological method is used to parametrise deviation from randomness in fragment size spectra. 相似文献
18.
Baggio L Cavinato M Cherubini R Conzato M Cucinotta F Favaretto S Gerardi S Lora S Stoppa P Williams JR 《Radiation protection dosimetry》2002,99(1-4):211-214
Protons and alpha particles of high linear energy transfer (LET) have shown an increased relative biological effectiveness (RBE) with respect to X/gamma rays for several cellular and molecular endpoints in different in vitro cell systems. To contribute to understanding the biochemical mechanisms involved in the increased effectiveness of high LET radiation, an extensive study has been designed. The present work reports the preliminary result of this study on two human tumoural cell lines, DLD1 and HCT116, (with different p53 status), which indicate that for these cell lines, p53 does not appear to take a part in the response to radiation induced DNA damage, suggesting an alternative p53-independent pathway and a cell biochemical mechanism dependent on the cell type. 相似文献
19.
Aloke Chatterjee 《Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment》1989,280(2-3):439-448
Fundamental studies in radiation biology with high-LET charged particles involve a systematic study of the physical, chemical, molecular and cellular processes. Water molecules and DNA present inside a cell constitute the important targets for energy deposition which eventually lead to either cell death or mutation or transformation. High-LET charged particles are very efficient in causing these types of damages. One of the primary lesions for causing injury to a cell is the production of DNA strand breaks. A good understanding of these breaks is essential before ultimate biological effects of heavy particles can be predicted. Based on known molecular mechanisms of the formation of strand breaks, a theoretical model is presented along with a comparison between the predictions of the model and experimental data. The studies have shown that LET is not a convenient physical parameter to relate the extent of strand breaks and one needs to know the microscopic distribution of energy (track structure). A discussion has also been presented to provide a background on various radiobiological characteristics of high-LET charged particles from the point of view of their uniqueness in damaging cancer cells. 相似文献
20.
ATM-dependent cellular response to DNA double strand breaks plays a pivotal role in the maintenance of the integrity of the genome. Upon irradiation, activated ataxia-telangiectasia mutated (ATM) proteins phosphorylate various downstream mediators and effectors, such as histone H2AX, MDC1, 53BP1 and NBS1. These proteins create discrete foci within the nuclei, which are detectable under fluorescence microscopes. Interestingly, the size of the foci is also increasing as increasing the time after irradiation. Particularly, the residual foci form large foci, the sizes of which reach approximately 2 μm in diameter. We confirmed that such 'foci growth' is a mechanism, by which DNA damage signal is amplified. Especially, a proper DNA damage response of cells to lower doses of ionising radiation required amplification of the ATM-dependent damage signal by recruiting the DNA damage checkpoint factors to the site of chromatin. 相似文献