The role of nitric oxide synthase activity in connection with induced resistance against low-dose hyper-radiosensitivity
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE41483 | GEO | 2013/04/15
SECONDARY ACCESSION(S): PRJNA177169
REPOSITORIES: GEO
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Project description:The cells harvested for microarray analysis were high-dose rate (HDR) irradiated, low-dose rate (LDR) irradiated or unirradiated T-47D cells. The HDR-irradiated cells were harvested 24h after a dose of 0.3 Gy at 35 Gy/h, a time where hyper-radiosensitivity (HRS) had returned. The HRS-deficient LDR-irradiated cells were harvested 2 months after a dose of 0.3 Gy at 0.3 Gy/h. LDR-irradiated vs. Control (unirradiated) contains 4 biological replicates. HDR- vs. LDR-irradiated contains 3 biological replicates. HDR-irradiated vs. Control contains 4 biological replicates.
2013-04-15 | E-GEOD-41483 | biostudies-arrayexpress
Project description:Hyper-radiosensitivity (HRS) is the increased sensitivity to low doses of ionizing radiation 12 observed in most cell lines. We previously demonstrated that HRS is permanently abolished in cells irradiated at a low dose rate (LDR), in a mechanism dependent on transforming growth factor β3 (TGF-β3). In this study, we aimed to elucidate the activation and receptor binding of TGF-β3 in this mechanism. T-47D cells were pre-treated with inhibitors of potential receptors and activators of TGF-β3, along with addition of small extracellular vesicles (sEVs) from LDR primed cells, before their radiosensitivity was assessed by the clonogenic assay. The protein content of sEVs from LDR primed cells was analyzed with mass spectrometry. Our results show that sEVs contain TGF-β3 regardless of priming status, but only sEVs from LDR primed cells remove HRS in reporter cells. Inhibition of the matrix metalloproteinase (MMP) family prevents removal of HRS, suggesting an MMP-dependent activation of TGF-β3 in the LDR primed cells. We demonstrate a functional interaction between TGF-β3 and activin receptor like kinase 1 (ALK1), by showing that TGF-β3 removes HRS through ALK1 binding, independent of ALK5 and TGF-βRII. These results are an important contribution to a more comprehensive understanding of the mechanism behind TGF-β3 mediated removal of HRS.
2022-08-12 | PXD035010 | Pride
Project description:Purpose: The International Commission on Radiological Protection (ICRP) recently recommended reducing the occupational equivalent dose limit for the lens of the eye. Based primarily on a review of epidemiological data, the absorbed dose threshold is now considered to be 0.5 Gy for induction of acute opacities, reduced from the previous threshold of 2 Gy. However, direct mechanistic evidence to support an understanding of the underlying molecular mechanisms of damage is still lacking. To this end, we explored the effects of a broad dose-range of ionizing radiation exposure on gene expression changes in a human lens epithelial (HLE) cell-line in order to better understand the shape of the dose-response relationship and identify transcriptional thresholds of effects. Methods: HLE cells were exposed to doses of 0, 0.01, 0.05, 0.25, 0.5, 2, and 5 Gy of X-ray radiation at two dose rates (1.62 cGy/min and 38.2 cGy/min). Cell culture lysates were collected 20 h post-exposure and analysed using whole-genome RNA-sequencing. Pathways and dose-thresholds of biological effects were identified using benchmark dose (BMD) modeling. Results: Transcriptional responses were minimal at doses less than 2 Gy. At higher doses there were a significant number of differentially expressed genes (DEGs) (p < 0.05, fold change > |1.5|) at both dose rates, with 1308 DEGs for the low dose rate (LDR) and 840 DEGs for the high dose rate (HDR) exposure. Dose-response modeling showed that a number of genes exhibited non-linear bi-phasic responses, which was verified by digital droplet PCR. BMD analysis showed the majority of the pathways responded at BMD median values in the dose range of 1.5-2.5 Gy, with the lowest BMD median value being 0.6 Gy for the HDR exposure. The minimum pathway BMD median value for LDR exposure, however, was 2.5 Gy. Although the LDR and HDR exposures shared pathways involved in extracellular matrix reorganization and collagen production with BMD median value of 2.9 Gy, HDR exposures were more effective in activating pathways associated with DNA damage response, apoptosis, and cell cycling relative to LDR exposure. Conclusion: Overall, the results suggest that radiation induces complex non-linear transcriptional dose-response relationships that are dose-rate dependent. Pathways shared between the two dose rates may be important contributors to radiation-induced cataractogenesis. BMD analysis suggests that the majority of pathways are activated above 0.6 Gy, which supports current ICRP identified dose thresholds for deterministic effects to the lens of the eye of 0.5 Gy.
2018-10-04 | GSE120805 | GEO
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. Data consist of 48 samples, representing 6 independent samples each from 3 doses delivered as either acute or low dose rate x-rays, plus 12 controls representing both acute and low dose rate sham treatments.
2015-05-14 | E-GEOD-62623 | biostudies-arrayexpress
Project description:Although radiation effects have been extensively studied, the biological effects of low-dose radiation (LDR) are controversial. This study investigates LDR-induced alterations in locomotive behavior and gene expression profiles of Drosophila melanogaster. We measured locomotive behavior using larval pupation height and rapid iterative negative geotaxis (RING) assay after exposure to 0.1 Gy gamma-radiation (dose rate of 16.7 mGy/h). We also observed chronic LDR effects on development (pupation and eclosion rates) and longevity (life span). To identify chronic LDR effects on gene expression, we performed whole-genome expression analysis using gene-expression microarrays, and confirmed the results using quantitative real-time PCR. Pupation height was significantly higher after LDR treatment at the first larval instar. Locomotive behavior of male flies was significantly greater approximately 3M-BM--5 weeks after LDR, but pupation and eclosion rates and life spans were not significantly different. Genome-wide expression analysis identified 344 genes that were differentially expressed in irradiated larvae compared with those of controls. We identified several genes belonging to larval behavior functional groups such as locomotive behavior and oxidation reduction, and genes involved in conventional functional groups modulated by irradiation such as defense response, sensory and perception. Four candidate genes were confirmed as differentially expressed genes in irradiated larvae using qRT-PCR. These data suggest that LDR stimulates locomotion-related genes, and these genes can be used as potential markers for LDR. Eggs were collected from 5-day-old female flies and cultivated for 24 h on standard medium. Then, twenty larvae were manually selected and seeded on fresh standard medium in a new vial. After transfer, the experimental group of first-instar larvae was immediately irradiated with chronic gamma-radiation at a dose rate of 16.7 mGy/h. After treatment, gamma-irradiated flies and non-irradiated control flies were maintained in the same incubator at 25degC.
2014-09-26 | E-GEOD-61759 | 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:In the event of an improvised nuclear device (IND), a complex IR exposure will occur consisting of both low (LDR) and high-dose rates (HDR). We have previously addressed LDR exposures from internal emitters or externally deposited radionuclides on biofluid small molecule signatures, but further research on the HDR component is required. Here, we exposed 8 − 10 week old male C57BL/6 mice to a cumulative dose of 3 Gy using a reference dose rate of 0.7 Gy/min or a HDR of 7 Gy/sec, collected urine and serum at 1 and 7 d, then compared the metabolite signatures using an untargeted (urine) approach with liquid chromatography mass spectrometry platforms.
2022-04-15 | ST002176 | MetabolomicsWorkbench
Project description:In the event of an improvised nuclear device (IND), a complex IR exposure will occur consisting of both low (LDR) and high-dose rates (HDR). We have previously addressed LDR exposures from internal emitters or externally deposited radionuclides on biofluid small molecule signatures, but further research on the HDR component is required. Here, we exposed 8 − 10 week old male C57BL/6 mice to a cumulative dose of 3 Gy using a reference dose rate of 0.7 Gy/min or a HDR of 7 Gy/sec, collected urine and serum at 1 and 7 d, then compared the metabolite signatures using either untargeted (urine) or targeted (serum) approaches with liquid chromatography mass spectrometry platforms.
2022-04-14 | ST002175 | MetabolomicsWorkbench
Project description:The role of RB1 in response to radiation was examined in human osteoblasts. We demonstrate that RB1 induced SASP genes, a response which was attenuated in RB1 knockdown osteoblasts. Subconfluent hOB shEV and shRB1 cells were irradiated at 4 Gy using a 137Cesium source at a dose rate of 1.7 min/Gy and cell pelllets collected 0, 2, 4, 8, 16 and 24 hrs after irradiation.
2013-09-14 | E-GEOD-50532 | biostudies-arrayexpress
Project description:Although radiation effects have been extensively studied, the biological effects of low-dose radiation (LDR) are controversial. This study investigates LDR-induced alterations in locomotive behavior and gene expression profiles of Drosophila melanogaster. We measured locomotive behavior using larval pupation height and rapid iterative negative geotaxis (RING) assay after exposure to 0.1 Gy gamma-radiation (dose rate of 16.7 mGy/h). We also observed chronic LDR effects on development (pupation and eclosion rates) and longevity (life span). To identify chronic LDR effects on gene expression, we performed whole-genome expression analysis using gene-expression microarrays, and confirmed the results using quantitative real-time PCR. Pupation height was significantly higher after LDR treatment at the first larval instar. Locomotive behavior of male flies was significantly greater approximately 35 weeks after LDR, but pupation and eclosion rates and life spans were not significantly different. Genome-wide expression analysis identified 344 genes that were differentially expressed in irradiated larvae compared with those of controls. We identified several genes belonging to larval behavior functional groups such as locomotive behavior and oxidation reduction, and genes involved in conventional functional groups modulated by irradiation such as defense response, sensory and perception. Four candidate genes were confirmed as differentially expressed genes in irradiated larvae using qRT-PCR. These data suggest that LDR stimulates locomotion-related genes, and these genes can be used as potential markers for LDR.
2014-09-26 | GSE61759 | GEO