Gene expression response in human peripheral blood exposed to mixed neutron-photon radiation ex vivo
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA453396 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:In the current global scenario there is always a possibility that a terrorist group might acquire material to produce a nuclear device. In the likelihood of a detonation of an improvised nuclear device (IND) the prompt radiation would consist of both photons (gamma rays) and neutrons. As neutrons generally have a high Relative Biological Effectiveness (RBE) for most physiological endpoints, it is important to understand the impact that neutrons would have on the biodosimetry methods that are being developed for medical triage purposes. We have previously reported transcriptomic response in human and mouse blood to neutron exposure and determined its RBE compared to photons for gene induction. In this report, we studied the effect of mixed neutron-photon radiation on gene expression in human peripheral blood in order to mimic an IND type radiation observed increase in number as well as expression level of genes with increasing percentage of neutron in mixed exposures which peaked at 25% neutron exposure which was maximum neutron percentage used for the study. We identified 156 genes that responded significantly to all the neutron-photon mixed exposures. These genes were found to be mainly involved in p53 signaling and DNA damage response. The 25% neutron exposure also showed maximum enrichment of known neutron associated gene ontology terms reported in the previous studies. Analysis of upstream regulators of gene expression showed strong activation of TP53, SLC29A1, PDCD1 and suppression of ANLN, AURK and ANXA2 across all exposures. While AGT was exclusively activated by neutron specific exposures. We confirmed the expression of genes which showed increased expression as a function of increased neutron percentage using quantitative real-time RT-PCR which matched with the microarray data. Thus, the data in this current study clearly indicates that gene expression can be used to estimate the percentage of the neutron component in mixed neutron-photon exposures.
2020-09-02 | GSE113611 | GEO
Project description:Background: Radiation exposure due to the detonation of an improvised nuclear device remains a major security concern. Radiation from such a device involves a combination of photons and neutrons. Although photons will make the greater contribution to the total dose, neutrons will certainly have an impact on the severity of the exposure as they have high relative biological effectiveness. Results: We investigated the gene expression signatures in the blood of mice exposed to 3 Gy x-rays, 0.75 Gy of neutrons, or to mixed field photon/neutron with the neutron fraction contributing 5%, 15%, or 25% of a total 3 Gy radiation dose. Gene ontology and pathway analysis revealed that genes involved in protein ubiquitination pathways were significantly overrepresented in all radiation doses and qualities. On the other hand, eukaryotic initiation factor 2 (EIF2) signaling pathway was identified as one of the top 10 ranked canonical pathways in neutron, but not pure x-ray, exposures. In addition, the related mTOR and regulation of EIF4/p70S6K pathways were also significantly underrepresented in the exposures with a neutron component, but not in x-ray radiation. The majority of the changed genes in these pathways belonged to the ribosome biogenesis and translation machinery and included several translation initiation factors (e.g. Eif2ak4, Eif3f), as well as 40S and 60S ribosomal subunits (e.g. Rsp19, Rpl19, Rpl27). Many of the differentially downregulated ribosomal genes (e.g. RPS19, RPS28) have been causally associated with human bone marrow failure syndromes and hematologic malignancies. We also observed downregulation of transfer RNA processes, in the neutron-only exposure (p < 0.005). Ingenuity Pathway Analysis (p < 0.05) of differentially expressed genes predicted significantly suppressed activity of the upstream regulators c-Myc and Mycn, transcription factors known to control ribosome biogenesis. Conclusions: We describe the gene expression profile of mouse blood following exposure to mixed field neutron/x-ray irradiation. We have discovered that pathways related to protein translation are significantly underrepresented in the exposures containing a neutron component. Our results highlight the significance of neutron exposures that even the smallest percentage can have profound biological effects that will affect medical management and treatment decisions in case of a radiological emergency.
2018-06-15 | GSE113509 | GEO
Project description:In the present study approximately 1 to 2 mm3 prostate tumor AT1 was inoculated subcutaneously in the right hind leg of adult male Copenhagen rats. When the tumor diameter exceeded 15 mm, tumors of 5 and 4 rats were irradiated with carbon ion radiation of 37 or 16Gy respectively. Tumors of 5 other rats were irradiated with photon radiation of 37Gy. One animal irradiated with 37 Gy carbon ion radiation and one animal irradiated with photon radiation was sacrificed 12h, 30h, 72h, 7d and 14d after irradiation respectively. One animal irradiated with 16 Gy photon radiation was sacrificed 12h, 60h, 7d and 14d after irradiation respectively. Non-irradiated animals were sacrificed at 60h time point. Tumors were dissected and frozen in liquid nitrogen immediately. Total RNA from tumor material was isolated using the NucleoSpin RNA L kit (#740962.20, Macherey-Nagel). Differential gene expression analysis was performed on the Agilent whole rat genome Oligo Microarray (44k) platform by comparative two dye hybridisation with dye-swaps.
2008-07-18 | E-TABM-481 | biostudies-arrayexpress
Project description:Identification of differentially expressed genes and pathways in mice exposed to mixed field neutron/x-ray radiation
| PRJNA451468 | ENA
Project description:Background: In the event of an improvised nuclear device detonation, the prompt radiation exposure would consist of γ rays plus a neutron component that would contribute to the total dose. As neutrons cause more complex and difficult to repair damage to cells that would result in more severe health burden to affected individuals, it is paramount to be able to estimate the contribution of neutrons to an estimated dose, to provide information for those making treatment decisions. Results: Mice exposed to either 0.25 or 1 Gy of neutron or 1 or 4 Gy x-ray radiation were sacrificed at 1 or 7 days after exposure. Whole genome microarray analysis identified 7,285 and 5,045 differentially expressed genes in the blood of mice exposed to neutron or x-ray radiation, respectively. Neutron exposure resulted in mostly downregulated genes, whereas x-rays showed both down- and up-regulated genes. A total of 34 differentially expressed genes were regulated in response to all ≥1 Gy exposures at both times. Of these, 25 genes were consistently downregulated at days 1 and 7, whereas 9 genes, including the transcription factor E2f2, showed bi-directional regulation; being downregulated at day 1, while upregulated at day 7. Gene ontology analysis revealed that genes involved in nucleic acid metabolism processes were persistently downregulated in neutron irradiated mice, whereas genes involved in lipid metabolism were upregulated in x-ray irradiated animals. Most biological processes significantly enriched at both timepoints were consistently represented by either under- or over-expressed genes. In contrast, cell cycle processes were significant among down-regulated genes at day 1, but among up-regulated genes at day 7 after exposure to either neutron or x-rays. Cell cycle genes downregulated at day 1 were mostly distinct from the cell cycle genes upregulated at day 7. However, five cell cycle genes, Fzr1, Ube2c, Ccna2, Nusap1, and Cdc25b, were both downregulated at day 1 and upregulated at day 7. Conclusions: We describe, for the first time, the gene expression profile of mouse blood cells following exposure to neutrons. We have found that neutron radiation results in both distinct and common gene expression patterns compared with x-ray radiation.
2017-02-01 | GSE85323 | GEO
Project description:RNA-seq of rat NSCs stimulated with lithium and/or photon radiation.
| PRJEB29008 | ENA
Project description:The detonation of an improvised nuclear device would produce prompt radiation consisting of both photons (gamma-rays) and neutrons. While much effort in recent years has gone into the development of radiation biodosimetry methods suitable for mass triage, the possible effect of neutrons on the endpoints studied has remained largely uninvestigated. We have used a novel neutron irradiator with an energy spectrum based on that 1-1.5 km from the epicenter of the Hiroshima blast to begin examining the effect of neutrons on global gene expression, and the impact this may have on the development of gene expression signatures for radiation biodosimetry. We have exposed peripheral blood from healthy human donors to 0, 0.1, 0.3, 0.5, or 1 Gy of neutrons ex vivo using our neutron irradiator, and compared the transcriptomic response 24 h later to that resulting from exposure to 0.1, 0.3, 0.5, 1, 2 or 4 Gy of photons (x-rays).
2017-02-22 | GSE90909 | GEO
Project description:It is elusive whether clonal selection of tumor cells in response to ionizing radiation (IR) is a deterministic or stochastic process. With high resolution clonal barcoding and tracking of over 400.000 HNSCC patient-derived tumor cells the clonal dynamics of tumor cells in response to IR was analysed. Fractionated IR induced a strong selective pressure for clonal reduction. This significantly exceeded uniform clonal survival probabilities indicative for a strong clone-to clone difference. within tumor cells. Survival to IR is driven by a deterministic clonal selection of a smaller population which commonly survives radiation, while increased clonogenic capacity is a result of clonal competition of cells which have been selected stochastically. The ratio of these parameters is amenable to radiation sensitivity which correlates to prognostic biomarkers of HNSCC. Evidence for the existence of a rare subpopulation with an intrinsically radiation resistant phenotype was found at a frequency of 0.6-3.3%. With cellular barcoding we introduce a novel functional heterogeneity associated qualitative readout for evaluating the contribution of stochastic and deterministic clonal selection processes in response to IR. To analyze transcriptomic changes of HNSCC cell lines after fractionated Photon IR (5x4Gy), RNAseq analysis was performed on irradiated cells in comparison to untreated control cells (EBI submission E-MTAB-9693)
2021-08-31 | E-MTAB-10685 | biostudies-arrayexpress
Project description:CGH was used to compare induced structural variation among soybean fast neutron lines, developed in background M92-220. 114 different soybean fast neutron lines were hybridized against the parental reference genotype M92-220. The soybean tiling array consists of 700k probes, spaced at approximately 1.1 kb intervals.
2011-08-01 | E-GEOD-31038 | biostudies-arrayexpress
Project description:CGH was used to compare induced structural variation among soybean fast neutron lines, developed in background M92-220. 11 different soybean fast neutron lines were hybridized against the parental reference genotype M92-220. The soybean tiling array consists of 700k probes, spaced at approximately 1.1 kb intervals.
2011-08-02 | E-GEOD-31111 | biostudies-arrayexpress