Response of the EPI-200 human 3-D skin model to high and low doses of protons
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE16935 | GEO | 2011/07/01
SECONDARY ACCESSION(S): PRJNA117647
REPOSITORIES: GEO
Similar Datasets
Project description:Accumulating data suggest that the biological responses to high and low doses of radiation are qualitatively different, necessitating the direct study of low dose responses. Most such studies have utilized 2-dimensional culture systems, which may not fully represent responses in 3-dimensional tissues. To gain insight into low dose responses in tissue, we have profiled global gene expression in EPI-200, a 3-dimensional tissue model from MatTek that imitates the structure and function of human epidermis, at 4, 16 and 24 hours after exposure to high (2.5 Gy) and low (0.1 Gy) doses of low LET protons. Untreated controls and samples exposed to 10 cGy or to 2.5 Gy were analyzed at three different times (4, 16 or 24 hours after exposure). Three biological repeats were performed for each condition
2011-07-01 | E-GEOD-16935 | biostudies-arrayexpress
Project description:Accumulating data suggest that the biological responses to high and low doses of radiation are qualitatively different, necessitating the direct study of low dose responses. Most such studies have utilized 2-dimensional culture systems, which may not fully represent responses in 3-dimensional tissues. To gain insight into low dose responses in tissue, we have profiled global gene expression in EPI-200, a 3-dimensional tissue model that imitates the structure and function of human epidermis, at 4, 16 and 24 hours after exposure to high (2.5 Gy) and low (0.1 Gy) doses of low LET protons. The most significant gene ontology groups among genes altered in expression were consistent with effects observed at the tissue level, where the low dose was associated with gradual recovery and tissue remodeling, while the high dose resulted in loss of structural integrity and terminal differentiation. Network analysis of the significantly responding genes suggested that TP53 dominated the response to 2.5 Gy, while HNF4A, a novel transcription factor not previously associated with radiation response, was most prominent in the low dose response. Thus, these studies address the molecular basis of response to low versus high dose low LET radiation exposure. Radiation induced gene expression in 3-dimensional tissue model, Epi-200, was measured at 4, 16 and 24 hours after exposure to doses of 0, 0.1 and 2.5 Gy of protons. Three independent experiments were performed in the each time (4, 16 and 24 hours) using one tissue sample per a data point.
2010-06-08 | E-GEOD-20629 | biostudies-arrayexpress
Project description:Accumulating data suggest that the biological responses to high and low doses of radiation are qualitatively different, necessitating the direct study of low dose responses. Most such studies have utilized 2-dimensional culture systems, which may not fully represent responses in 3-dimensional tissues. To gain insight into low dose responses in tissue, we have profiled global gene expression in EPI-200, a 3-dimensional tissue model that imitates the structure and function of human epidermis, at 4, 16 and 24 hours after exposure to high (2.5 Gy) and low (0.1 Gy) doses of low LET protons. The most significant gene ontology groups among genes altered in expression were consistent with effects observed at the tissue level, where the low dose was associated with gradual recovery and tissue remodeling, while the high dose resulted in loss of structural integrity and terminal differentiation. Network analysis of the significantly responding genes suggested that TP53 dominated the response to 2.5 Gy, while HNF4A, a novel transcription factor not previously associated with radiation response, was most prominent in the low dose response. Thus, these studies address the molecular basis of response to low versus high dose low LET radiation exposure.
2010-06-01 | GSE20629 | GEO
Project description:Biological response X-rays traditionally serves as a standard in comparative analysis of different qualities of ionizing radiation. Most such studies have utilized 2-dimensional culture systems, which may not fully represent responses in 3-dimensional tissues. To gain insight into biological responses to X-rays in tissue, we have profiled global gene expression in EPI-200, a 3-dimensional tissue model that imitates the structure and function of human epidermis, at 4, 16 and 24 hours after exposure to 2.5 Gy of X-rays. The most significant gene ontology groups were associated with cell cycle, cytokinesis, establishment and maintenance of chromatin architecture. Remarkably, genes with a role in cell cycle were predominantly downregulated at all time points while genes involved in the cell defense response - upregulated. Methyltransferases were predominantly upregulated at 4 and 16h while transcription factors - at 16h and 24h suggesting remodeling of the chromatin. Among the genes with a role in signal transduction, irradiation affected kinase modulators and microtubule binding motor proteins at all time points. Kinases, especially non-receptor serine/threonine protein kinases were predominantly upregulated at 16 and 24h suggesting a rearrangement in the signaling pathways. The results also confirm involvement in the biological response of the genes participating in p53 pathway that were overrepresented at 4 and 16h in the set of upregulated genes and ubiquitin proteasome pathway that were predominantly downregulated at 16h and 24h In the same time, growing numbers of altered in expression genes: 449 at 4h; 720 and 3986 genes - at 16 and 24h postirradiation, accordingly suggested that ionizing radiation caused long term changes in the gene expression the exceeded the time frame proposed for this study. Radiation induced gene expression in 3-dimensional tissue model, Epi-200, was measured at 4, 16 and 24 hours after exposure to the dose of 2.5 Gy of X-rays. Three independent experiments were performed in the each time point using one tissue sample per a data point.
2011-08-30 | E-GEOD-23807 | biostudies-arrayexpress
Project description:Global gene expression responses to low doses of protons in a human 3-dimensional skin model
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Project description:The impact of low-dose ionizing radiation (IR) on human brain has recently attracted attention due to increased use of IR for diagnostic purposes. The aim of this study was to investigate low-dose radiation response in hippocampus. Female C57Bl/6 mice were irradiated with 0 (control), 0.063, 0.125 or 0.5 Gy and quantitative label-free proteomic analysis of hippocampus was performed after 24 months. Key pathways were validated by immunoblotting. CREB signaling and CREB-associated pathways were the most affected ones at all doses. The two lower doses seemed to induce CREB pathway, whereas the exposure to 0.5 Gy deactivated CREB. Similarly, the lowest dose (0.063 Gy) was anti-inflammatory reducing the number of activated microglia (IBA1), whilst induction of activated microglia and reactive astroglia (GFAP) was found at 0.5 Gy suggesting increased inflammation and astrogliosis, respectively. Apoptotic markers BAX and cleaved CASP-3 and oxidative stress markers (carbonylation, NRF-2) were increased only at the highest dose. Since activated CREB pathway plays a central role in learning and memory, these data suggest neuroprotection at the lowest dose (0.063 Gy) but neurodegeneration at 0.5 Gy. These effects become significant only in old animals (24 m) and support the hypothesis of radiation-induced accelerated aging in the brain.
2019-11-06 | PXD015729 | Pride
Project description:Dose-dependent (phospho) proteome responses of mouse embyronic stem cells to ionising radiation. Quantitative SILAC- and mass spectrometry-based proteomics and phosphoproteomics experiments were performe at half an hour (0.5h) and four hours (4h) after exposure to LD (0.1 Gy) and high doses (HD; 1 Gy) of IR.
2022-03-18 | PXD025343 | Pride
Project description:We studied the radiation effect on cell culture model of oral mucositis. The musositis model (tissues) used is an organotypic model which consisted of 3-dimensional (3-D) cell cultures of primary human oral keratinocytes. The tissues were purchased from MatTek corporation (Ashland, MA) and were grown on top of microporous membrane and supplemented with MatTek serum free media. These tissues were irradiated with 12 Gy. Six hours after the irradiation the tissues were cut in half. Half of the tissue was used to extract total RNA (RNeasy Plus Mini kit, Qiagen, Germantown, MD) and the other half was used to evaluate the histology and the apoptosis. We had the following groups: Non-Irradiated Tissue, Irradiated Tissue with 12 Gy; Irradiated Tissue with 12 Gy pretreated with N-acetylcysteine (NAC); Irradiated Tissue with 12 Gy pretreated with the Traditional Chinese Medicine Qingre-Liyan decoction (QYD); and Irradiated Tissue with 12 Gy pretreated with 50:50 w/w NAC-QYD.
2014-10-16 | GSE62397 | GEO
Project description:Biological response X-rays traditionally serves as a standard in comparative analysis of different qualities of ionizing radiation. Most such studies have utilized 2-dimensional culture systems, which may not fully represent responses in 3-dimensional tissues. To gain insight into biological responses to X-rays in tissue, we have profiled global gene expression in EPI-200, a 3-dimensional tissue model that imitates the structure and function of human epidermis, at 4, 16 and 24 hours after exposure to 2.5 Gy of X-rays. The most significant gene ontology groups were associated with cell cycle, cytokinesis, establishment and maintenance of chromatin architecture. Remarkably, genes with a role in cell cycle were predominantly downregulated at all time points while genes involved in the cell defense response - upregulated. Methyltransferases were predominantly upregulated at 4 and 16h while transcription factors - at 16h and 24h suggesting remodeling of the chromatin. Among the genes with a role in signal transduction, irradiation affected kinase modulators and microtubule binding motor proteins at all time points. Kinases, especially non-receptor serine/threonine protein kinases were predominantly upregulated at 16 and 24h suggesting a rearrangement in the signaling pathways. The results also confirm involvement in the biological response of the genes participating in p53 pathway that were overrepresented at 4 and 16h in the set of upregulated genes and ubiquitin proteasome pathway that were predominantly downregulated at 16h and 24h In the same time, growing numbers of altered in expression genes: 449 at 4h; 720 and 3986 genes - at 16 and 24h postirradiation, accordingly suggested that ionizing radiation caused long term changes in the gene expression the exceeded the time frame proposed for this study.
2011-08-31 | GSE23807 | GEO
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