title: Repeated exposure of human fibroblasts to ionizing radiation reveals an adaptive response that is not mediated by interleukin-6 or TGF-β.
abstract: Exposing cells to a low dose can protect them against a subsequent higher exposure. This phenomenon is known as adaptive response and is frequently observed in a variety of cells. Even though similarities are suspected with other non-targeted effects, such as bystander effects, the exact mechanism behind adaptive response is not fully clarified. In this study human primary fibroblasts were tested for their response to ionizing radiation (IR) after administrating a low priming dose (0.1-0.5Gy). Both the abundance of γH2AX as a marker for double-stranded breaks and the levels of cytokines, secreted in the medium, were monitored in time. Upon challenge, IR-primed cells showed modified γH2AX spot size distributions and altered repair kinetics, consistent with an adaptive response. In addition, 24h after priming with IR, four cytokines were significantly upregulated in the medium - GM-CSF (1.33×); IL6 (4.24×); IL8 (1.33×); TGF-β (1.46×). In order to mimick the protective effect of IR priming, we primed the cells with either IL6 or TGF-β. This did not elicit an altered γH2AX response as observed in IR-primed cells, indicating that the adaptive response in these primary fibroblasts is regulated in an IL-6 and TGF-β independent manner.
authors.affiliation: Bio-imaging and Cytometry Unit, Department of Molecular Biotechnology, Ghent University, Coupure Links 653, 9000 Gent, Belgium. birger.dieriks@ugent.be
authors.forename: Birger
authors.initials: B
authors.lastname: Dieriks
authors.forename: Winnok
authors.initials: W
authors.lastname: De Vos
authors.forename: Sarah
authors.initials: S
authors.lastname: Baatout
authors.forename: Patrick
authors.initials: P
authors.lastname: Van Oostveldt
mesh_terms: D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D004307:Dose-Response Relationship, Radiation; D005347:Fibroblasts / Q000528:radiation effects*; D006657:Histones / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
chemical_list: D016207:Cytokines; C468783:H2AX protein, human; D006657:Histones; D015850:Interleukin-6; D016212:Transforming Growth Factor beta