Gene expression in mouse blood following low dose-rate or acute x-ray exposure
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Sally Amundson
PROVIDER: E-GEOD-62623 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:The aim of the present study is to analyze by microarray techniques how gene expression is modulated after exposure to low and very low doses of ionizing radiation, to evaluate if the pattern of gene expression shows dose dependence, and to search for putative regulatory mechanisms behind the observed gene-expression modifications.For this, whole blood samples from five healthy donors diluted in IMDM (1:10) were exposed at six doses between 5 and 500 mGy. Total RNA extraction from CD4+ lymphocytes was done at four different post-irradiation times (150, 300, 450 and 600 min). After mRNA amplification, aRNAs were hybridized on 4x44k DNA microarrays. The results indicated that up-regulation were twice than down-regulation. Surprisingly, the number of modulated genes doesnM-bM-^@M-^Yt seem to change drastically with dose, even at the lowest dose of 5 mGy. Clustering analysis revealed seven gene expression clusters with different dose dependence profiles. The functional analysis showed that the genes which increased their expression with the dose were related to p53 pathway and DNA damage response. This could be observed from 25 mGy, but becomes very clear at doses equal or greater than 100 mGy. On the other hand, genes with a constant modulation of their expression in all the tested doses were related to cellular respiration, ATP metabolic process and chromatin organization. These latter molecular mechanisms seem to be triggered at very low doses (5-25 mGy). In-silico promoter analysis seems to confirm the implication of transcription factors related to the pathways mentioned above. Human whole blood samples from 5 healthy donors were diluted in IMDM medium (1:10) and exposed to 500,100,50,25,10 and 5 mGy of Cobalt 60 gamma-rays. Gene expression alterations were measured 150, 300, 450 and 600 min post exposure after negative cell sorting of lymphocytes TCD4+ cells.
2013-06-24 | E-GEOD-43151 | biostudies-arrayexpress
Project description:Radiation biodosimetry can play a critical role in the response to a large-scale radiologic emergency, and gene expression profiles have shown promise for providing biodosimetric information. This study was designed to test if gene expression could be used to distinguish between doses received from acute exposures and more protracted exposures, such as those that would result from fallout. Mice were exposed to whole body X-rays at low dose rate (LDR, 3.09 mGy/min) for 6, 12, or 24 hours (1.1, 2.2, or 4.4 Gy), or to equivalent doses delivered at high dose rate (HDR, 1.03 Gy/min). Global gene expression was measured in their blood 24 h after the start of exposure, and genes with the potential to classify samples by radiation dose and dose rate were identified.
2015-05-14 | GSE62623 | GEO
Project description:Analysis of human peripheral blood 48 hours after irradiation ex vivo with graded doses of gamma rays. Results have been used in building and testing classifiers to predict exposure dose for use in radiological triage, and also provide insight into immune cell responses. Results were compared with those from earlier times and from patients exposed in vivo. Peripheral blood from 5 healthy donors was exposed ex vivo to 0. 0.5, 2, 5, or 8 Gy gamma-rays and gene expression was analyzed up to 48 hours after exposure.
2013-09-11 | E-GEOD-44201 | biostudies-arrayexpress
Project description:Background: The effects of dose-rate and its implications on radiation biodosimetry methods are not well studied in the context of large-scale radiological scenarios. There are significant health risks to individuals exposed to an acute dose in such an event, but the most realistic scenario would be a combination of exposure to both high and low dose-rates, from both external and internal radioactivity. It is important therefore, to understand the biological response to prolonged exposure; and further, discover biomarkers that can be used to estimate the extent of damage from low-dose rate exposure and propose appropriate clinical treatment. Methods: We irradiated human whole blood ex vivo to three doses, 0.56 Gy, 2.25 Gy and 4.45 Gy, using two dose rates: 1.1Gy/min and 3.1mGy/min. After 24 hours, we isolated RNA from blood cells and hybridized these to Agilent Whole Human genome microarrays. We validated the microarray results using qRT-PCR. Results: Microarray results showed that there were 454 significantly differentially expressed genes after prolonged exposure to all doses. After acute exposure, 598 genes were differentially expressed to all doses combined. Gene ontology terms enriched in both sets of genes were related to immune processes and B cell mediated immunity. Genes responding to acute exposure was also enriched in functions related to natural killer cell activation and cell-to-cell signaling. As expected, p53 pathway was found to be significantly enriched at all doses and by both dose-rates of radiation. Prediction algorithms were able to distinguish between low dose-rate and acute exposures, on the basis of a group of genes. These maybe candidates for preliminary testing as markers for differences in gene expression based on dose-rate. Radiation induced gene expression was measured in ex vivo irradiated human blood, at the 24hr time point after irradiation. Doses (0.56 Gy, 2.2 Gy and 4.45 Gy) were delivered by two dose rates, acute dose rate of 1Gy/min and low dose rate of 3.1 mGy/min.
2015-04-28 | E-GEOD-65292 | biostudies-arrayexpress
Project description:Baseline gene expression of human lymphocytes 24 hours after 5 Gy gamma irradiation We used microarrays to detail the global gene expression of human lymphocytes after irradiation Compare the gloable gene expression of human lymphocyte 24 hours after exposure to doses between 0 and 5 Gy γ rays
2013-04-01 | E-GEOD-44245 | biostudies-arrayexpress
Project description:Measuring global gene expression using cDNA or oligonucleotide microarrays is an effective approach to understanding the complex mechanisms of the effects of radiation. However, few studies have been carried out that investigate gene expression in vivo after prolonged exposure to low-dose-rate radiation. In this study, C57BL/6J mice were continuously irradiated with ?-rays for 485 days at dose-rates of 0.032 – 13 ?Gy/min. Gene expression profiles in the kidney and testis from irradiated and unirradiated mice were analyzed, and differentially expressed genes were identified. A combination of pathway analysis and hierarchical clustering of differentially expressed genes revealed that expression of genes involved in mitochondrial oxidative phosphorylation was elevated in the kidney after irradiation at the dose-rates of 0.65 ?Gy/min and 13 ?Gy/min. Expression of cell cycle-associated genes was not profoundly modulated in the kidney, in contrast to the response to acute irradiation, suggesting a threshold in the dose-rate for modulation of the expression of cell cycle-related genes in vivo following exposure to radiation. We demonstrated that changes to the gene expression profile in the testis were largely different from those in the kidney. The Gene Ontology categories “DNA metabolism”, “response to DNA damage” and “DNA replication” overlapped significantly with the clusters of genes whose expression decreased with an increase in the dose-rate to the testis. These observations provide a fundamental insight into the organ-specific responses to low-dose-rate radiation. Key Words: kidney, low-dose-rate, radiation, microarray, mitochondrial oxidative phosphorylation, testis 3 biological replicates for each experimental group were analysed. GSE14290_Kidney_raw_data.csv contains the raw data for GSM357146, GSM357425, GSM357426, GSM357452 to GSM357460. GSE14290_Testis_raw_data.csv contains the raw data for GSM357471 to GSM357482. In these files, the sample identifiers are included in the column headers.
2009-05-27 | E-GEOD-14290 | biostudies-arrayexpress
Project description:Linear energy transfer (LET) is an important factor affecting several aspects of the irradiation effect, e.g. cell survival and mutation frequency, making the heavy-ion beam an effective mutagen. To study the mechanisms behind LET-dependent effects, expression profiling was performed after heavy-ion beam irradiation of imbibed rice seeds. Array-based experiments at three time points (0.5, 1, 2 h after the irradiation) revealed that the number of up- or down-regulated genes was highest 2 h after irradiation. Array-based experiments with four different LETs at 2 h after irradiation identified LET-independent regulated genes that were up/down-regulated regardless of the value of LET; LET-dependently regulated genes, whose expression level increased with the rise of LET value, were also identified. Oryza sativa L. 'Nipponbare' seeds were imbibed for 3 days. The seeds were irradiated with 22.5 or 50 keV/μm C-ion at a dose of 15 Gy. Gene expressions of irradiated and unirradiated embryos were measured at 0.5, 1, and 2 hours after irradiation. Three independent experiments were performed at each time and LET.
2016-07-01 | E-GEOD-78997 | biostudies-arrayexpress
Project description:Linear energy transfer (LET) is an important factor affecting several aspects of the irradiation effect, e.g. cell survival and mutation frequency, making the heavy-ion beam an effective mutagen. To study the mechanisms behind LET-dependent effects, expression profiling was performed after heavy-ion beam irradiation of imbibed rice seeds. Array-based experiments at three time points (0.5, 1, 2 h after the irradiation) revealed that the number of up- or down-regulated genes was highest 2 h after irradiation. Array-based experiments with four different LETs at 2 h after irradiation identified LET-independent regulated genes that were up/down-regulated regardless of the value of LET; LET-dependently regulated genes, whose expression level increased with the rise of LET value, were also identified. Oryza sativa L. 'Nipponbare' seeds were imbibed for 3 days. The seeds were irradiated with 22.5 or 50 keV/μm C-ion or 63 or 80 keV/μm Ne-ion at a dose of 15 Gy. Gene expressions of irradiated and unirradiated embryos were measured at 2 hours after irradiation. Three independent experiments were performed at each time and LET.
2016-07-01 | E-GEOD-78994 | biostudies-arrayexpress
Project description:For around ten years, microarrays have been suggested for the diagnosis of ionizing radiation exposure. We assessed for the first time the relevance of gene expression profiling in a real accidental case. This study was performed on peripheral blood mononuclear cells of 41 potential victims. The different strategies of analysis highlighted a huge effect of the blood sample handling on the gene expression profiles. This effect was so high that it could mask specific modulations as a potential effect of ionizing radiation exposure. Thus, we assessed a new way of blood sampling adapted to gene expression analysis: PAXgene. With this method, more than 70% of the modulations of gene expression induced 3 hours after an ex vivo exposure to 0.5 Gy were preserved even in a 24-hour delayed analysis (as for transportation of blood sample from the accident location to the laboratory). We validated a new methodology in order to propose a new strategy of blood sampling and handling for gene profiling. This system could be used in case of accidental overexposure to study whether gene expression is a relevant biomarker of ionizing radiation exposure. Radiation induced gene expression in human blood was measured at 3 hours after exposure to doses of 0 and 0.5 grays. Following the incubation of 3 hours at 37°C, the RNA extractions were performed either immediately or 24h later (as for transportation of blood sample at room temperature). Two different blood preservation methods were compared: classical anticoagulant and PAXgene Blood RNA System. Venous blood samples of 6 donors were used (3 for anticoagulant study, 3 for Paxgene study). Each sample was hybridized twice.
2016-07-04 | E-GEOD-21240 | biostudies-arrayexpress
Project description:Expression profiles in mouse liver exposed to long-term gamma-irradiation were examined to assess in vivo effects of low dose-rate radiation. Three groups of male C57BL/6J mice were exposed to whole body irradiation at dose-rates of 17-20 mGy/day, 0.86-1.0 mGy/day or 0.042-0.050 mGy/day for 401-485 days (cumulative doses were approximately 8 Gy, 0.4 Gy or 0.02 Gy, respectively). Expression profiles were produced for RNA isolated from irradiated individual animals and for pooled RNA from sham-irradiated 3 animals for control. The expression levels of 6 irradiated animals for each dose were compared individually with those of 2 pooled controls (3 irradiated samples to one pooled control in first and second experiments). The experiments were conducted twice at similar dose-rates. In the first experiment, three groups of 8 weeks old male C57BL/6J mice were exposed to whole body irradiation at dose-rates of either 16.6 mGy/day (H1), 0.858 mGy/day (M1) or 0.042 mGy/day (L1) for 485 days (cumulative doses were 8030 mGy, 416 mGy or 20.6 mGy, respectively). In the second experiment, the doe-rates were slightly elevated as 20.0 mGy/day (H2), 1.000 mGy/day (M2) or 0.050 mGy/day (L2) for 401 days (doses were 8015 mGy, 401 mGy or 20 mGy, respectively). A group of control unirradiated mice were set for each experiment (C1, C2).
2011-01-01 | E-GEOD-20562 | biostudies-arrayexpress