Bystander response to 0.5 Gy of alpha-particles in a human 3-dimensional skin model in 16h after exposure to ionizing radiation
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE23899 | GEO | 2011/08/31
SECONDARY ACCESSION(S): PRJNA130551
REPOSITORIES: GEO
Similar Datasets
Project description:Ionizing radiation (IR) not only affects cells that are directly irradiated but also their non-irradiated neighbors, which show responses known as bystander effects. While bystander and direct responses have several common end points including apoptosis and micronucleation, chromatin remodeling and altered levels or activities of regulatory proteins, they can be quantitatively and qualitatively different. The majority of studies of radiation bystander effects have utilized 2-dimensional in vitro systems, but we have recently demonstrated such effects in EPI-200 (Mat-Tek, Ashland, MA), a 3-dimensional tissue model that precisely imitates the structure and function of human epidermis. Global gene expression is a powerful tool for uncovering both fundamental signaling processes and the mechanistic basis of cellular or physiological effects. By exposing only a thin strip across the center of the EPI-200 tissue, we have been able to measure global gene expression responses in bystander cells located at 0.125 and 0.625 um from the irradiation line, in 16h after irradiation. The data were analyzed using BRB-Array Tools (NIH), and further network analysis was performed with IPA (Ingenuity). Significantly responding genes were identified at the both distances. For instance, all sets demonstrated upregulation of two key enzymes of the lipid biosynthesis, UGT1 and PITPNB, and downregulation of proapoptotic proteins: BAX and ARHGEF5. In contrast, several proteins involved in transcriptional repression (CHD6, CHD8 andWRNIP1) were strongly upregulated suggesting a rearrangement in the gene transcription. These changes suggest an activation of bystander mechanisms different from those observed in 2-dimensional cell cultures. Radiation induced gene expression in 3-dimensional tissue model, Epi-200, was measured in 16 hours after exposure to 0.5 Gy of alpha-particles. Three independent experiments were performed for the samples collected at different distances from the irradiation line (125-625 and 625-1125 um) using three tissue fragments per a data point.
2011-08-30 | E-GEOD-23899 | biostudies-arrayexpress
Project description:Ionizing radiation (IR) not only affects cells that are directly irradiated but also their non-irradiated neighbors, which show responses known as bystander effects. While bystander and direct responses have several common end points including apoptosis and micronucleation, chromatin remodeling and altered levels or activities of regulatory proteins, they can be quantitatively and qualitatively different. The majority of studies of radiation bystander effects have utilized 2-dimensional in vitro systems, but we have recently demonstrated such effects in EPI-200 (Mat-Tek, Ashland, MA), a 3-dimensional tissue model that precisely imitates the structure and function of human epidermis. Global gene expression is a powerful tool for uncovering both fundamental signaling processes and the mechanistic basis of cellular or physiological effects. By exposing only a thin strip across the center of the EPI-200 tissue, we have been able to measure global gene expression responses in directly irradiated and bystander cells located at 0, 0.25, 0.5, 0.75 and 1mm from the irradiation line. The data were analyzed using BRB-Array Tools (NIH), and further network analysis was performed with IPA (Ingenuity). Significantly responding genes were identified at all distances and included sets common to both direct and bystander responses. For instance, all sets demonstrated upregulation of a major component of the drug metabolism pathway, CYP1B1, and downregulation of MMP1, an enzyme involved in degradation of extracellular matrix. In contrast, PTGS2, a gene strongly implicated in the bystander response was upregulated in directly irradiated tissues, but actually downregulated in bystander cells. This effect may be time dependent, but may also suggest activation of bystander signaling mechanisms different from those observed in 2-dimensional cell cultures. According to network analysis of our results, the genes responding in bystander tissue fell into 5 major categories: cell death, cell communication, cell differentiation, stress response, and response to wounding, suggesting active intracellular communication in bystander tissue. Radiation induced gene expression in 3-dimensional tissue model, Epi-200, was measured at 4 hours after exposure to 0.5 Gy of alpha-particles. Three independent experiments were performed for the samples collected at different distances from the irradiation line (250-500, 500-750 and 750-1000 micrometers) using three tissue fragments per a data point.
2011-08-30 | E-GEOD-23804 | biostudies-arrayexpress
Project description:Bystander mechanisms that originate in the areas surrounding a tissue damage presumably play an important role participating in wound healing and tissue remodeling. Thus, identification and characterization of bystander mechanisms will help to development of new treatments of patients with a radiation exposure. In the present study, we irradiated 3-dimensional tissue model of human epidermis, Epi-200 (Mat-Tek, Ashland, MA), with 2.5 Gy protons. By exposing only a thin strip across the center of the EPI-200 tissue, we have been able to measure global gene expression responses in directly irradiated and bystander cells located at 0.125-0.375, 0.375-0.625, 0.625-875 mm from the irradiation line. The data were analyzed using BRB-Array Tools (NIH), and further gene ontology analysis and network analysis was performed with Panther (Applied Biosystems) and IPA (Ingenuity), accordingly. Significantly responding genes were identified at all distances and included sets common to both direct and bystander responses. False discovery rate in bystander samples did not exceed 20% (p=0.001) and was sufficiently low in the samples obtained after the whole tissue exposure (0.06-1.16%). Analysis of the fragments cut at the same distance revealed 52, 54 and 88 differentially expressed genes. These gene lists overlapped each other had from 3 to 12 genes in common including CLED2, S100A7A. Samples obtained after the whole tissue exposure discovered 949 differentially expressed genes. Moreover, the performed gene ontology analysis showed there overrepresentation of TP53 pathway (pathways, p=2.04E-02), a common marker of direct irradiation response, and also overrepresentation of the following groups of genes: signal transduction (p=4.52E-04), cell communication (p=1.24E-04) and cell cycle in the category of biological processes; DNA helicase activity (p=2.54E-07), receptor binding (p=6.19E-04), calcium ion binding proteins (p=2.57E-03) as the molecular functions. Differentially expresses genes of bystander samples had few categories in common such as cell communication (p=2.36E-03) and signal transduction (p=2.42E-03) among the biological processes and receptor activity (p=4.54E-03) among the molecular functions. Categories specific for the bystander samples included G-protein coupled receptors (p=7.24E-03) and ligand-gated ion channels (p=4.16E-03) suggesting a role of external stimulation and ion trafficking in bystander mechanisms. Radiation induced gene expression in 3-dimensional tissue model, Epi-200, was measured in 16 hours after exposure to 2.5 Gy of protons. Four independent experiments were performed for the samples collected at different distances from the irradiation line (125-375, 375-625 and 625-875 micrometers) using three tissue fragments per a data point. Moreover, three sets of whole tissue irradited samples were also generated for 0 and 2.5 Gy (6 samples total) and used for comparison of bystander and direct responses.
2011-08-30 | E-GEOD-23803 | biostudies-arrayexpress
Project description:Ionizing radiation (IR) not only affects cells that are directly irradiated but also their non-irradiated neighbors, which show responses known as bystander effects. While bystander and direct responses have several common end points including apoptosis and micronucleation, chromatin remodeling and altered levels or activities of regulatory proteins, they can be quantitatively and qualitatively different. The majority of studies of radiation bystander effects have utilized 2-dimensional in vitro systems, but we have recently demonstrated such effects in EPI-200 (Mat-Tek, Ashland, MA), a 3-dimensional tissue model that precisely imitates the structure and function of human epidermis. Global gene expression is a powerful tool for uncovering both fundamental signaling processes and the mechanistic basis of cellular or physiological effects. By exposing only a thin strip across the center of the EPI-200 tissue, we have been able to measure global gene expression responses in directly irradiated and bystander cells located at 0, 0.25, 0.5, 0.75 and 1mm from the irradiation line. The data were analyzed using BRB-Array Tools (NIH), and further network analysis was performed with IPA (Ingenuity). Significantly responding genes were identified at all distances and included sets common to both direct and bystander responses. For instance, all sets demonstrated upregulation of a major component of the drug metabolism pathway, CYP1B1, and downregulation of MMP1, an enzyme involved in degradation of extracellular matrix. In contrast, PTGS2, a gene strongly implicated in the bystander response was upregulated in directly irradiated tissues, but actually downregulated in bystander cells. This effect may be time dependent, but may also suggest activation of bystander signaling mechanisms different from those observed in 2-dimensional cell cultures. According to network analysis of our results, the genes responding in bystander tissue fell into 5 major categories: cell death, cell communication, cell differentiation, stress response, and response to wounding, suggesting active intracellular communication in bystander tissue.
2011-08-31 | GSE23804 | GEO
Project description:Bystander mechanisms that originate in the areas surrounding a tissue damage presumably play an important role participating in wound healing and tissue remodeling. Thus, identification and characterization of bystander mechanisms will help to development of new treatments of patients with a radiation exposure. In the present study, we irradiated 3-dimensional tissue model of human epidermis, Epi-200 (Mat-Tek, Ashland, MA), with 2.5 Gy protons. By exposing only a thin strip across the center of the EPI-200 tissue, we have been able to measure global gene expression responses in directly irradiated and bystander cells located at 0.125-0.375, 0.375-0.625, 0.625-875 mm from the irradiation line. The data were analyzed using BRB-Array Tools (NIH), and further gene ontology analysis and network analysis was performed with Panther (Applied Biosystems) and IPA (Ingenuity), accordingly. Significantly responding genes were identified at all distances and included sets common to both direct and bystander responses. False discovery rate in bystander samples did not exceed 20% (p=0.001) and was sufficiently low in the samples obtained after the whole tissue exposure (0.06-1.16%). Analysis of the fragments cut at the same distance revealed 52, 54 and 88 differentially expressed genes. These gene lists overlapped each other had from 3 to 12 genes in common including CLED2, S100A7A. Samples obtained after the whole tissue exposure discovered 949 differentially expressed genes. Moreover, the performed gene ontology analysis showed there overrepresentation of TP53 pathway (pathways, p=2.04E-02), a common marker of direct irradiation response, and also overrepresentation of the following groups of genes: signal transduction (p=4.52E-04), cell communication (p=1.24E-04) and cell cycle in the category of biological processes; DNA helicase activity (p=2.54E-07), receptor binding (p=6.19E-04), calcium ion binding proteins (p=2.57E-03) as the molecular functions. Differentially expresses genes of bystander samples had few categories in common such as cell communication (p=2.36E-03) and signal transduction (p=2.42E-03) among the biological processes and receptor activity (p=4.54E-03) among the molecular functions. Categories specific for the bystander samples included G-protein coupled receptors (p=7.24E-03) and ligand-gated ion channels (p=4.16E-03) suggesting a role of external stimulation and ion trafficking in bystander mechanisms.
2011-08-31 | GSE23803 | GEO
Project description:The radiation bystander effect has been documented with multiple endpoints in various models. While many of the factors regulating this response are known, the mechanisms are still not well understood, and even less is known about signaling of bystander responses in 3-dimensional (3D) tissues. We have used the EPI-200 3D epidermal tissue model to measure global gene expression changes in bystander tissue in order to gain insight into the molecular pathways involved. We identified 187 genes with significantly altered expression in the region between 250 μm and 1 mm from the site of irradiation four hours after exposure. Gene expression at 250-500 μm and 500-750 μm was similar to that within the first 250 μm, the region that also included the directly irradiated tissue. Gene expression, although still significantly altered, began to return toward control levels in the region between 750 μm and 1 mm, however, suggesting a spatial limit to the bystander signal. The 3D bystander genes were concentrated in gene ontology classifications associated with direct irradiation, such as regulation of cell cycle progression and cell death, as well as categories previously associated with bystander responses, such as extracellular signaling, inflammatory processes, and terminal differentiation.
2016-09-10 | GSE32541 | GEO
Project description:The bystander effect from ionizing radiation consists of cellular responses generated from unirradiated cells to the irradiation of their neighbors. The bystander effect can lead to DNA damage and genomic instability in the affected cells. This non-targeted effect of radiation has received attention due to its potential implications for cancer therapy and radiation protection. Although studied extensively, a complete understanding of its molecular mechanism is the subject of ongoing research. While many studies have targeted specific factors which are suggested to be involved in the bystander effect, few have looked at whole genome gene expression in bystander cells. Furthermore, even fewer studies have looked at the expression in noncancerous human cell lines. In this study we have used a genome-wide microarray approach to investigate transcriptional responses in irradiated and bystander immortalized human fibroblasts following 0.1 Gy ?-particle irradiation. Total RNA was isolated from F11hTERT fibroblasts irradiated with 0.1 Gy ?-particles and bystander fibroblasts receiving medium from control (sham irradiated) and irradiated cells (0.1 Gy). RNA was isolated 4, 8 and 26 h after irradiation.
2011-09-13 | E-GEOD-32091 | biostudies-arrayexpress
Project description:The bystander effect from ionizing radiation consists of cellular responses generated from non-irradiated cells to the irradiation of their neighbors. The bystander effect is predominant at low doses and can lead to DNA damage and genomic instability in the affected cells. This non-targeted effect of radiation has received attention due to its potential implications for cancer therapy and radiation protection. Although studied extensively, a complete understanding of its molecular mechanism is the subject of ongoing research. While many studies have targeted specific factors which are suggested to be involved in the bystander effect, few have looked at whole genome gene expression in bystander cells. Furthermore, even fewer studies have looked at the expression in normal human cell lines. In this study, we have monitored transcriptional responses to γ-radiation in irradiated and bystander normal fibroblasts simultaneously using a genome-wide microarray approach. Bystander fibroblasts incubated in medium from irradiated cells, showed transient enrichment (less than 1.5 fold) in ribosome and oxidative phosphorylation pathways, and neurodegenerative disease pathways associated with mitochondrial dysfunctions. Bystander fibroblasts did not, however, display increases in oxidative stress, a phenomenon often linked with the radiation induced bystander effect. Total RNA was isolated from normal human fibroblasts irradiated with 2.0 Gy and fibroblasts incubated with medium from sham irradiated and irradiated cells 2 h after irradiation. RNA was isolated 4, 8 and 26 h after irradiation and there are 4 replicates for each sample for a total of 36 samples.
2010-12-03 | E-GEOD-25772 | biostudies-arrayexpress
Project description:Direct irradiation of 3-dimensional skin model, Epi-200, with alpha-particles led to differential regulation of 166 genes: 16 and 150 genes were differentially expressed at 1 and 16 h postirradiation. Unlike the traditional 2-dimensional in vitro systems, Epi-200 made of the primary cells, epidermal human keratinocytes. It mimics the structure of the human epidermis Global gene expression is a powerful tool for uncovering both fundamental signaling processes and the mechanistic basis of cellular or physiological effects. By comparing irradiated tissues with non-irradiated control, we have been able to measure global gene expression responses and reveal the affected biological pathways and molecular functions. The data were analyzed using BRB-Array Tools (NIH), and further gene ontology analysis was performed with Panther database (Applied Biosystems). Gene ontology analysis of the samples harvested in 16h after exposure showed that irradiation presumably affected the genes involved in cell-cell signaling (15 genes, , p=9.0 x E-04) ion transport (10 genes, p=0.00189) and amino acid metabolism (5 genes, p=0.0258). Among 16 genes differentially expressed in 1h after exposure we found NOTCH2 (ENST00000401649) and methyltransferase AOF1 (KDM1B). In the mammalian cells, NOTCH signaling pathway has a role in differentiation and intracellular communication. Moreover the intercellular domain of NOTCH regulates gene expression acting as a transcription factor. In turn, AOF1 affects the transcription via histone demethylation. Thus, irradiation with alpha-particles caused predominant downregulation of multiple genes in 1 and 16h after exposure. It also suggested that changes in cell metabolism initially affected transcriptional regulation and finally led to the rearrangement in expression of genes playing a role in biosynthesis and ion trafficking. Radiation induced gene expression in 3-dimensional tissue model, Epi-200, was measured in 1 and 16 h hours after exposure to 0.5 Gy of alpha-particles. Three independent experiments were performed using one tissue sample per a data point.
2011-08-30 | E-GEOD-23901 | biostudies-arrayexpress
Project description:The bystander effect from ionizing radiation consists of cellular responses generated from non-irradiated cells to the irradiation of their neighbors. The bystander effect can lead to DNA damage and genomic instability in the affected cells. This non-targeted effect of radiation has received attention due to its potential implications for cancer therapy and radiation protection. Although studied extensively, a complete understanding of its molecular mechanism is the subject of ongoing research. While many studies have targeted specific factors which are suggested to be involved in the bystander effect, few have looked at whole genome gene expression in bystander cells. Furthermore, even fewer studies have looked at the expression in normal human cell lines. In this study, we have monitored transcriptional responses to γ-radiation in irradiated and bystander normal fibroblasts simultaneously using a genome-wide microarray approach. In this study we have investigated the transcriptional response in F11hTERT fibroblasts irradiated with 2 Gy, 2 hours after irradiation.
2010-12-03 | GSE25772 | GEO