title: Transcriptome Alterations In X-Irradiated Human Gingiva Fibroblasts.
abstract: 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.
authors.affiliation: *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.
authors.forename: Robert
authors.initials: R
authors.lastname: Weissmann
authors.forename: Tim
authors.initials: T
authors.lastname: Kacprowski
authors.forename: Michel
authors.initials: M
authors.lastname: Peper
authors.forename: Jennifer
authors.initials: J
authors.lastname: Esche
authors.forename: Lars R
authors.initials: LR
authors.lastname: Jensen
authors.forename: Laura
authors.initials: L
authors.lastname: van Diepen
authors.forename: Matthias
authors.initials: M
authors.lastname: Port
authors.forename: Andreas W
authors.initials: AW
authors.lastname: Kuss
authors.forename: Harry
authors.initials: H
authors.lastname: Scherthan
mesh_terms: D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology* / Q000528:radiation effects*; D005786:Gene Expression Regulation / Q000502:physiology / Q000528:radiation effects; D005881:Gingiva / Q000502:physiology* / Q000528:radiation effects*; D006801:Humans; D011829:Radiation Dosage; D011836:Radiation Tolerance / Q000502:physiology / Q000528:radiation effects; D059467:Transcriptome / Q000502:physiology* / Q000528:radiation effects*; D014965:X-Rays