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| Status |
Public on Aug 31, 2011 |
| Title |
Bystander response to 2.5 Gy of protons in a human 3-dimensional skin model in 16 h after exposure |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
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.
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| Overall design |
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.
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| Contributor(s) |
Amundson SA, Mezentsev AV |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
Aug 25, 2010 |
| Last update date |
Feb 22, 2018 |
| Contact name |
Alexandre Mezentsev |
| E-mail(s) |
am2710@columbia.edu
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| Phone |
(212) 305-2166
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| Fax |
(212) 305-7391
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| Organization name |
Columbia University
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| Department |
Dermatology
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| Street address |
630 west 168th Street, VC 15-204
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| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10031 |
| Country |
USA |
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| Platforms (1) |
| GPL4133 |
Agilent-014850 Whole Human Genome Microarray 4x44K G4112F (Feature Number version) |
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| Samples (30)
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| GSM587099 |
Tissue_model_Epi_200_0Gy_125_375_um_rep1 |
| GSM587100 |
Tissue_model_Epi_200_0Gy_375_625_um_rep1 |
| GSM587101 |
Tissue_model_Epi_200_0Gy_625_875_um_rep1 |
| GSM587102 |
Tissue_model_Epi_200_2.5Gy_125_375_um_rep1 |
| GSM587103 |
Tissue_model_Epi_200_2.5Gy_375_625_um_rep1 |
| GSM587104 |
Tissue_model_Epi_200_0.5Gy_625_875_um_rep1 |
| GSM587105 |
Tissue_model_Epi_200_0Gy_125_375_um_rep2 |
| GSM587106 |
Tissue_model_Epi_200_0Gy_375_625_um_rep2 |
| GSM587107 |
Tissue_model_Epi_200_0Gy_625_875_um_rep2 |
| GSM587108 |
Tissue_model_Epi_200_2.5Gy_125_375_um_rep2 |
| GSM587109 |
Tissue_model_Epi_200_2.5Gy_375_625_um_rep2 |
| GSM587110 |
Tissue_model_Epi_200_0.5Gy_625_875_um_rep2 |
| GSM587111 |
Tissue_model_Epi_200_0Gy_125_375_um_rep3 |
| GSM587112 |
Tissue_model_Epi_200_0Gy_375_625_um_rep3 |
| GSM587113 |
Tissue_model_Epi_200_0Gy_625_875_um_rep3 |
| GSM587114 |
Tissue_model_Epi_200_2.5Gy_125_375_um_rep3 |
| GSM587115 |
Tissue_model_Epi_200_2.5Gy_375_625_um_rep3 |
| GSM587116 |
Tissue_model_Epi_200_0.5Gy_625_875_um_rep3 |
| GSM587117 |
Tissue_model_Epi_200_0Gy_125_375_um_rep4 |
| GSM587118 |
Tissue_model_Epi_200_0Gy_375_625_um_rep4 |
| GSM587119 |
Tissue_model_Epi_200_0Gy_625_875_um_rep4 |
| GSM587120 |
Tissue_model_Epi_200_2.5Gy_125_375_um_rep4 |
| GSM587121 |
Tissue_model_Epi_200_2.5Gy_375_625_um_rep4 |
| GSM587122 |
Tissue_model_Epi_200_0.5Gy_625_875_um_rep4 |
| GSM587123 |
Tissue_model_Epi_200_0Gy_whole_tissue_rep1 |
| GSM587124 |
Tissue_model_Epi_200_0Gy_whole_tissue_rep2 |
| GSM587125 |
Tissue_model_Epi_200_0Gy_whole_tissue_rep3 |
| GSM587126 |
Tissue_model_Epi_200_2.5Gy_whole_tissue_rep1 |
| GSM587127 |
Tissue_model_Epi_200_2.5Gy_whole_tissue_rep2 |
| GSM587128 |
Tissue_model_Epi_200_2.5Gy_whole_tissue_rep3 |
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| Relations |
| BioProject |
PRJNA130697 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE23803_RAW.tar |
239.1 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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