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1.
A multicolor banding (mBAND) fluorescence in situ hybridization technique was used to investigate the presence inhuman populations of a stable biomarker-intrachromosomal chromosome aberrations-of past exposure to high-LET radiation. Peripheral blood lymphocytes were taken from healthy Russian nuclear workers occupationally exposed from 1949 onward to either plutonium, gamma rays or both. Metaphase spreads were produced and chromosomes 1 and 2 were hybridized with mBAND FISH probes and scored for intra-chromosomal aberrations. A large yield of intrachromosomal aberrations was observed in both chromosomes of the individuals exposed to high doses of plutonium, whereas there was no significant increase over the (low) background control rate in the population who were exposed to high doses of gamma rays.Interchromosome aberration yields were similar in both the high plutonium and the high gamma-ray groups. These results for chromosome 1 and 2 confirm and extend data published previously for chromosome 5. Intrachromosomal aberrations thus represent a potential biomarker for past exposure to high-LET radiations such as alpha particles and neutrons and could possibly be used as a biodosimeter to estimate both the dose and type of radiation exposure in previously exposed populations.  相似文献   

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A. V. Akleyev 《Biophysics》2010,55(1):128-141
Reviewed are radiobiological data on the emergence of tissue reactions that may determine the course and outcome of human chronic irradiation. The main mechanisms of the reaction of hemopoietic, immune, reproductive, endocrine, respiratory systems and skin to long-term and fractionated exposure to ionizing radiation are considered. The problem of developing a new approach to threshold dose estimation for chronic exposure effects is discussed.  相似文献   

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Ionizing radiation commonly used in the radiotherapy of brain tumours can cause adverse side effects to surrounding normal brain tissue. The most significant response of adult brain to radiation damage is induction of apoptosis. The adult mammalian subventricular zone (SVZ) of the brain lateral ventricles (LV) and their subsequent lateral ventricular extension, the rostral migratory stream (RMS), is one of the few areas, which retains the ability to generate new neurons and glial cells throughout life. Taking into account the fact, that ionizing radiation is one of the strongest exogenous factors affecting cell proliferation, the aim of the present study was to investigate the occurrence of radiation-induced apoptosis in this neurogenic region. Adult male Wistar rats were investigated 1, 5 or 10 days after single whole-body gamma irradiation with the dose of 3 Gy. Apoptotic cell death was determined by in situ labelling of DNA nick ends (TUNEL) and fluorescence microscopy evaluation of TUNEL-positive cells. Considerable increase of apoptotic TUNEL-positive cells was observed 24 hrs after irradiation in caudal parts of RMS; i.e. in the vertical arm and elbow of RMS. Initial increase was followed by strong reduction of apoptosis in the RMS and by secondary over-accumulation of apoptotic cells in the animals that survived ten days after exposure. Results showed, that the proliferating population of cells, arisen in SVZ are highly sensitive to radiation-induced apoptosis. This observation should have implications for clinical radiotherapy to avoid complications in therapeutic brain irradiation.  相似文献   

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The effect of the tetrapeptide tuftcin (Thr-Lys-Pro-Arg) on the humoral immune response in CBA mice exposed to sublethal irradiation in a dose of 450 sGy was studied. The drug was injected intraperitoneally for 5 days before (series I) or after (series II) radiation exposure. It has been shown that taftcin has no protective action but decreases considerably the immune response lowering due to radiation.  相似文献   

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So far, only a few studies investigated occupational exposure to ionizing radiation in pregnancy to cause birth defects (BDs). No association between BDs and ionizing radiation, although described for high-dose exposure, could ever be confirmed for employees, or specific job titles. Here, an explorative analysis of a prospective population-based birth cohort used to quantify the prevalence of BDs in infants between 1/2007 and 2/2008 is presented. An active examination of all livebirths by specially trained paediatricians in two defined areas was performed. Additionally, a study-specific questionnaire distributed among all becoming mothers in the surveyed regions included questions on maternal occupational exposure to ionizing radiation within the first trimester of pregnancy. In 3,816 births (including 165 infants with BDs; 4.3%), maternal answers concerning possible exposures to medical and occupational ionizing radiation were available. Relative risk (RR) estimates in mothers surveyed for occupational exposure to ionizing radiation (wearing a radiation dosimeter) and BDs in the offspring were calculated exploratively. A higher prevalence of infants with BDs (n = 4; 13.8%) was documented in newborns of the 29 surveyed mothers compared to that in 3,787 births from unexposed mothers (n = 161; 4.3%), corresponding to a RR of 3.2 (1.2–8.7). Excluding deformations, the RR increased to 4.0 (1.5–10.7). Adjustment for possible confounders did not change the results substantially.  相似文献   

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We have tested chronic exposure to 90Y beta radiation for its action as a complete tumor promoter, a stage I tumor promoter, or a stage II tumor promoter in SENCAR mouse skin. In skin initiated with a single application of 7,12,dimethylbenz[a]anthracene (DMBA, 10 nmol), chronic exposure to beta radiation as a complete promoter (0.5 Gy, twice/week, 13 weeks) produced no tumors and, when added to a complete chemical promoter (TPA), reduced tumor frequency about 30%. A similar result was observed when beta radiation was tested as a stage II promoter. DMBA-initiated mice that received chemical (12-O-tetradecanoylphorbol-13-acetate, TPA) stage I promotion followed by 13 weeks of beta-radiation exposure (0.5 Gy, twice/week) as stage II promotion produced essentially no tumors, and combining the same chronic beta-radiation exposure with chemical (mezerein) stage II promotion reduced tumor frequency about 20% when compared to a similar group that was not irradiated. Chronic beta-radiation exposure was tested two ways as a stage I tumor promoter in initiated skin that was subsequently treated with mezerein as a stage II promoter. Stage I promotion was shown to proceed with the passage of time, indicating this process occurs naturally in the absence of chemical or physical stimulation. Hyperthermia, previously shown to be a potent inhibitor of chemically stimulated stage I promotion, had no effect on the natural process, indicating at least some differences in mechanism between the two processes. The natural process was, in fact, inhibited by chemical tumor promoters, but not by radiation. In addition to the increase resulting from this natural process, tumor frequency was further increased slightly but significantly (12-15%, P less than or equal to 0.05) when chronic radiation exposure was given as a stage I promoter (0.5 Gy, twice/week, 13 weeks) subsequent to initiation, in spite of the expected 20% reduction resulting from this dose. Exposure of initiated animals to radiation (0.5 or 1.0 Gy, twice/week, 2 weeks) in addition to TPA as stage I promotion produced a similar increase in tumor frequency (P less than 0.02). At higher radiation doses, however, tumor frequency was reduced compared to unirradiated controls. In a third test as a stage I promoter, beta radiation (0.5 Gy twice/week, 4 weeks) was given prior to initiation with N-methyl-N'-nitro-N-nitrosoguanidine in animals subsequently promoted by TPA (twice/week, 13 weeks), and again the radiation slightly but significantly (P less than 0.03) increased tumor frequency compared to the unirradiated control group.(ABSTRACT TRUNCATED AT 400 WORDS)  相似文献   

9.
While the association between exposure to ionizing radiation and cancer is well established, its association with schizophrenia is unclear. The aim of our study was to assess risk of schizophrenia after childhood exposure to ionizing radiation to the head (mean dose: 1.5 Gy). The study population included an exposed group of 10,834 individuals irradiated during childhood for treatment of tinea capitis in the 1950s and two unexposed comparison groups of 5392 siblings and 10,834 subjects derived from the National Population Registry individually matched to the exposed group by age, sex (when possible), country of birth, and year of immigration to Israel. These groups were followed for a median 46 years for diagnosis of schizophrenia updated to December 2002. The Cox proportional hazards model stratified by matched sets was used to compare the risk of schizophrenia between the groups. Based on 1,217,531 person-years of follow-up, 451 cases were identified. No statistically significant association was found between radiation exposure and schizophrenia for the total group (hazard ratio per 1 Gy to the brain: 1.05, 95% confidence interval: 0.93-1.18) or within subgroups of sex, dose categories or latent period. When comparing a subgroup of subjects irradiated under 5 years of age with the matched unexposed group, the estimated hazard ratio reached 1.18 (95% confidence interval: 0.96-1.44; P = 0.1). The results of our analysis do not support an association between exposure to ionizing radiation and risk of schizophrenia. More research on possible effects of early exposure to ionizing radiation on schizophrenia specifically and brain tissue in general is needed.  相似文献   

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There is a need for novel and effective prophylactic treatments and radioprotective materials to protect civilians and military personnel from ionizing radiation in contaminated environments. Melanin, a naturally occurring, ubiquitous pigment, has been shown to confer radioresistance, acting as a potential radioprotective agent. We have demonstrated that melanized Cryptococcus neoformans (CN) cells had improved survival post ionizing irradiation than non-melanized ones. The goal of this study was to identify morphological changes in melanized and non-melanized CN cells following irradiation with densely-ionizing deuterons and alpha particles relative to sparsely-ionizing gamma radiation. We observed significant differences between the melanized and non-melanized CN cellular ultrastructure following irradiation. Melanized CN cells were relatively resistant to mid and max-dose levels of alpha particles and deuterons irradiation. Following irradiation the capsule was stripped, but the cell wall was intact and structural integrity was maintained. At the maximum dose, cytoplasmic vacuolization, and mitochondrial swelling started to occur. In contrast, the non-melanized CN strain was sensitive to the mid-dose radiation. Non-melanized cells presented two morphologies: small condensed, and swollen, lacking structural integrity. This morphological investigation provides the first direct evidence of the radioprotective properties of melanin in CN cells subjected to high RBE and high LET ionizing radiation.  相似文献   

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Monte Carlo simulation techniques were used to calculate the probability that thymine radical anions (T.-), formed by the slowing-down of high-energy protons in oriented DNA, will undergo a secondary protonation reaction. By assuming a large asymmetry in the thermal conductivity of oriented DNA fibres we predict a significant enhancement of protonation of T.- when the proton flux is incident on the sample parallel to the orientation of the DNA. These results are in qualitative agreement with experimental data on the production of TH. radicals when oriented DNA is exposed to fast neutrons.  相似文献   

14.

Introduction

Due to dangers associated with potential accidents from nuclear energy and terrorist threats, there is a need for high-throughput biodosimetry to rapidly assess individual doses of radiation exposure. Lipidomics and metabolomics are becoming common tools for determining global signatures after disease or other physical insult and provide a “snapshot” of potential cellular damage.

Objectives

The current study assesses changes in the nonhuman primate (NHP) serum lipidome and metabolome 7 days following exposure to ionizing radiation (IR).

Methods

Serum sample lipids and metabolites were extracted using a biphasic liquid–liquid extraction and analyzed by ultra performance liquid chromatography quadrupole time-of-flight mass spectrometry. Global radiation signatures were acquired in data-independent mode.

Results

Radiation exposure caused significant perturbations in lipid metabolism, affecting all major lipid species, including free fatty acids, glycerolipids, glycerophospholipids and esterified sterols. In particular, we observed a significant increase in the levels of polyunsaturated fatty acids (PUFA)-containing lipids in the serum of NHPs exposed to 10 Gy radiation, suggesting a primary role played by PUFAs in the physiological response to IR. Metabolomics profiling indicated an increase in the levels of amino acids, carnitine, and purine metabolites in the serum of NHPs exposed to 10 Gy radiation, suggesting perturbations to protein digestion/absorption, biological oxidations, and fatty acid β-oxidation.

Conclusions

This is the first report to determine changes in the global NHP serum lipidome and metabolome following radiation exposure and provides information for developing metabolomic biomarker panels in human-based biodosimetry.
  相似文献   

15.
A I Gaziev 《Radiobiologiia》1986,26(4):447-452
Mechanisms of induction of the antimutagenic and anticarcinogenic adaptive repair response of cells to the effect of alkylating substances and other genotoxic agents are discussed. The possibility of induction of adaptive repair response of mammalian cells to low-level radiation is suggested.  相似文献   

16.
Several authors have suggested that there is an excess risk of hyperparathyroidism, adenomas or hyperplasia after exposure to ionizing radiation. There is still, however, some uncertainty about this association, because these diseases are often asymptomatic and escape clinical detection if not specially searched for. This study is based on a pooled Swedish cohort of 27,925 persons with skin hemangiomas. The majority received radiation treatment in infancy between 1920 and 1965 in Stockholm and Gothenburg. The mean age at treatment was 6 months and the median thyroid dose was 0.20 Gy (range 0-28.5 Gy). Record linkage with the Swedish Cancer Register for the period 1958-1997 gave 43 cases of parathyroid adenoma in the cohort. Analyses of excess relative risk (ERR) models were performed using Poisson regression methods. Clinical records were scrutinized to determine if the childhood radiation exposure was known (biased cases) at the time of diagnosis. Seven of the cases of parathyroid adenoma were classified as biased cases. The standardized incidence ratio (SIR) was 2.10 (95% confidence interval 1.52-2.82) when all cases were included and 1.76 (95% CI 1.23-2.43) with the biased cases excluded. A linear dose-response model with stratification for sex fitted the data best. The ERR per gray was 3.84 (95% CI 1.56-8.99) with all cases and 1.56 (95% CI 0.36-4.45) with the biased cases excluded. There was a significant difference in the ERR per gray between the two subcohorts, probably because of different diagnostic activity in the regions. Our findings confirm that there is a dose-response relationship for radiation-induced parathyroid adenomas.  相似文献   

17.
Acute changes in the gene expression profile in mouse brain after exposure to ionizing radiation were studied using microarray analysis. RNA was isolated at 0.25, 1, 5 and 24 h after exposure to 20 Gy and at 5 h after exposure of the whole brain of adult mice to 2 or 10 Gy. RNA was hybridized onto 15K cDNA microarrays, and data were analyzed using GeneSpring and Significant Analysis of Microarray. Radiation modulated the expression of 128, 334, 325 and 155 genes and ESTs at 0.25, 1, 5 and 24 h after 20 Gy and 60 and 168 at 5 h after 2 and 10 Gy, respectively. The expression profiles showed dose- and time-dependent changes in both expression levels and numbers of differentially modulated genes and ESTs. Seventy-eight genes were modulated at two or more times. Differentially modulated genes were associated with 12 different classes of molecular function and 24 different biological pathways and showed time- and dose-dependent changes. The change in expression of four genes (Jak3, Dffb, Nsep1 and Terf1) after irradiation was validated using quantitative real-time PCR. Up-regulation of Jak3 was observed in another mouse strain. In mouse brain, there was an increase of Jak3 immunoreactivity after irradiation. In conclusion, changes in the gene profile in the brain after irradiation are complex and are dependent on time and dose, and genes with diverse functions and pathways are modulated.  相似文献   

18.
An increased risk of carcinogenesis caused by exposure to space radiation during prolonged space travel is a limiting factor for human space exploration. Typically, astronauts are exposed to low fluences of ionizing particles that target only a few cells in a tissue at any one time. The propagation of stressful effects from irradiated to neighboring bystander cells and their transmission to progeny cells would be of importance in estimates of the health risks of exposure to space radiation. With relevance to the risk of carcinogenesis, we investigated, in model C3H 10T½ mouse embryo fibroblasts (MEFs), modulation of the spontaneous frequency of neoplastic transformation in the progeny of bystander MEFs that had been in co-culture 10 population doublings earlier with MEFs exposed to moderate doses of densely ionizing iron ions (1 GeV/nucleon) or sparsely ionizing protons (1 GeV). An increase (P<0.05) in neoplastic transformation frequency, likely mediated by intercellular communication through gap junctions, was observed in the progeny of bystander cells that had been in co-culture with cells irradiated with iron ions, but not with protons.  相似文献   

19.
Quantitative regularities of recovery of wild-type diploid yeast cells irradiated with gamma-rays (60Co) simultaneously with exposure to high temperatures were studied. It was shown that in conditions of such a combined action the constant of recovery did not depend on the temperature at which the irradiation was carried out. However, with an increase of acting temperature an augmentation in the portion of irreversible component was registered. The analysis of cell inactivation revealed that the augmentation of the irreversible component was accompanied by a continuous increase of cell killing without any postirradiation division after which cells are incapable of recovery. The reproductive death was mainly exerted after ionizing radiation applied alone while in conditions of simultaneous thermoradiation action the interphase killing (cell death without division) predominated. It is concluded on this base that the mechanism of synergistic interaction of ionizing radiation and hyperthermia may be related with cardinal change in mechanisms of cell killing.  相似文献   

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A new model of the hematopoietic system response in humans chronically exposed to ionizing radiation describes the dynamics of the hematopoietic stem cell compartment as well as the dynamics of each of the four blood cell types (lymphocytes, neutrophiles, erythrocytes, and platelets). The required model parameters were estimated based on available results of human and experimental animal studies. They include the steady-state number of hematopoietic stem cells and peripheral blood cell lines in an unexposed organism, amplification parameters for each blood line, parameters describing proliferation and apoptosis, parameters of feedback functions regulating the steady-state numbers, and characteristics of radiosensitivity related to cell death and non-lethal cell damage. The model predictions were tested using data on hematological measurements (e.g., blood counts) performed in 1950–1956 in the Techa River residents chronically exposed to ionizing radiation since 1949. The suggested model of hematopoiesis is capable of describing experimental findings in the Techa River Cohort, including: (1) slopes of the dose–effect curves reflecting the inhibition of hematopoiesis due to chronic ionizing radiation, (2) delay in effect of chronic exposure and accumulated character of the effect, and (3) dose-rate patterns for different cytopenic states (e.g., leukopenia, thrombocytopenia).  相似文献   

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