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| Status |
Public on Aug 31, 2011 |
| Title |
Biological response to low dose of alpha-particles in a human 3-dimensional skin model, in 1 and 16h after exposure to ionizing radiation. |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
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.
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| Overall design |
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.
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| Contributor(s) |
Amundson SA, Mezentsev AV |
| Citation missing |
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| Submission date |
Aug 31, 2010 |
| Last update date |
Feb 22, 2018 |
| Contact name |
Alexandre Mezentsev |
| E-mail(s) |
am2710@columbia.edu
|
| Phone |
(212) 305-2166
|
| Fax |
(212) 305-7391
|
| Organization name |
Columbia University
|
| Department |
Dermatology
|
| Street address |
630 west 168th Street, VC 15-204
|
| 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 (12)
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| Relations |
| BioProject |
PRJNA130549 |
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