Transcriptome Alterations In X-Irradiated Human Gingiva Fibroblasts
Autor: | Harry Scherthan, Lars Riff Jensen, Andreas W. Kuss, Tim Kacprowski, Laura van Diepen, Robert Weissmann, Matthias Port, Michel Peper, Jennifer Esche |
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Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
radiation radiation effects repair Epidemiology DNA damage Health Toxicology and Mutagenesis Gingiva Biology Radiation Dosage Bioinformatics Radiation Tolerance Transcriptome 03 medical and health sciences 0302 clinical medicine Radioresistance microRNA Humans Radiology Nuclear Medicine and imaging KEGG Cells Cultured Regulation of gene expression cellular x rays Dose-Response Relationship Drug X-Rays Wnt signaling pathway Fibroblasts Cell cycle 030104 developmental biology Gene Expression Regulation 030220 oncology & carcinogenesis Papers Cancer research genetic effects |
Zdroj: | Health Physics |
ISSN: | 0017-9078 |
Popis: | Ionizing radiation is known to induce genomic lesions, such as DNA double strand breaks, whose repair can lead to mutations that can modulate cellular and organismal fate. Soon after radiation exposure, cells induce transcriptional changes and alterations of cell cycle programs to respond to the received DNA damage. Radiation-induced mutations occur through misrepair in a stochastic manner and increase the risk of developing cancers years after the incident, especially after high dose radiation exposures. Here, the authors analyzed the transcriptomic response of primary human gingival fibroblasts exposed to increasing doses of acute high dose-rate x rays. In the dataset obtained after 0.5 and 5 Gy x-ray exposures and two different repair intervals (0.5 h and 16 h), the authors discovered several radiation-induced fusion transcripts in conjunction with dose-dependent gene expression changes involving a total of 3,383 genes. Principal component analysis of repeated experiments revealed that the duration of the post-exposure repair intervals had a stronger impact than irradiation dose. Subsequent overrepresentation analyses showed a number of KEGG gene sets and WikiPathways, including pathways known to relate to radioresistance in fibroblasts (Wnt, integrin signaling). Moreover, a significant radiation-induced modulation of microRNA targets was detected. The data sets on IR-induced transcriptomic alterations in primary gingival fibroblasts will facilitate genomic comparisons in various genotoxic exposure scenarios. |
Databáze: | OpenAIRE |
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