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Published on: January 30, 2018
Transcriptome Alterations In X-Irradiated Human Gingiva Fibroblasts.
Robert Weissmann1, Tim Kacprowski, Michel Peper
1*Department of Human Genetics, University Medicine Greifswald and Interfaculty Institute of Genetics and Functional Genomics, University of Greifswald, Greifswald, Germany; †Interfaculty Institute for Genetics and Functional Genomics, Department of Functional Genomics, University Medicine Greifswald, Germany; ‡Institut für Radiobiologie der Bundeswehr in Verbindung mit der Universität Ulm, München, Germany.
Ionizing radiation exposure causes DNA damage and mutations, increasing cancer risk. This study reveals radiation-induced fusion transcripts and gene expression changes in human fibroblasts, with repair time impacting outcomes more than dose.
Area of Science:
- Molecular Biology
- Genomics
- Radiation Biology
Background:
- Ionizing radiation induces DNA damage, including double-strand breaks, which can lead to mutations and affect cellular fate.
- Cellular responses to radiation involve transcriptional changes and cell cycle alterations to manage DNA damage.
- Radiation-induced mutations, arising from misrepair, elevate cancer risk, particularly after high-dose exposures.
Purpose of the Study:
- To analyze the transcriptomic response of primary human gingival fibroblasts to varying doses of x-ray radiation.
- To identify radiation-induced fusion transcripts and dose-dependent gene expression changes.
- To investigate the impact of repair interval duration on transcriptomic alterations post-irradiation.
Main Methods:
- Exposure of primary human gingival fibroblasts to increasing doses of acute high dose-rate x rays (0.5 and 5 Gy).
- Analysis of transcriptomic data at different repair intervals (0.5 h and 16 h) post-exposure.
- Application of principal component analysis and overrepresentation analyses (KEGG, WikiPathways) to identify significant biological pathways and gene expression changes.
Main Results:
- Discovery of several radiation-induced fusion transcripts.
- Identification of dose-dependent gene expression changes in 3,383 genes.
- Principal component analysis indicated that repair interval duration had a greater impact on transcriptomic profiles than radiation dose.
- Overrepresentation analyses highlighted pathways related to radioresistance (Wnt, integrin signaling) and detected modulation of microRNA targets.
Conclusions:
- Transcriptomic alterations in fibroblasts following ionizing radiation are complex and influenced by both dose and repair time.
- The findings provide insights into cellular responses to radiation damage and radioresistance mechanisms.
- The generated datasets serve as a valuable resource for comparative genomic studies in various genotoxic exposure scenarios.
