title: Exposure to Carbon Ions Triggers Proinflammatory Signals and Changes in Homeostasis and Epidermal Tissue Organization to a Similar Extent as Photons.
abstract: The increasing application of charged particles in radiotherapy requires a deeper understanding of early and late side effects occurring in skin, which is exposed in all radiation treatments. We measured cellular and molecular changes related to the early inflammatory response of human skin irradiated with carbon ions, in particular cell death induction and changes in differentiation and proliferation of epidermal cells during the first days after exposure. Model systems for human skin from healthy donors of different complexity, i.e., keratinocytes, coculture of skin cells, 3D skin equivalents, and skin explants, were used to investigate the alterations induced by carbon ions (spread-out Bragg peak, dose-averaged LET 100 keV/μm) in comparison to X-ray and UV-B exposure. After exposure to ionizing radiation, in none of the model systems, apoptosis/necrosis was observed. Carbon ions triggered inflammatory signaling and accelerated differentiation of keratinocytes to a similar extent as X-rays at the same doses. High doses of carbon ions were more effective than X-rays in reducing proliferation and inducing abnormal differentiation. In contrast, changes identified following low-dose exposure (≤0.5 Gy) were induced more effectively after X-ray exposure, i.e., enhanced proliferation and change in the polarity of basal cells.
authors.affiliation: Department of Biophysics, GSI Helmholtzzentrum für Schwerionenforschung , Darmstadt , Germany.
authors.forename: Palma
authors.initials: P
authors.lastname: Simoniello
authors.affiliation: Department of Biophysics, GSI Helmholtzzentrum für Schwerionenforschung, Darmstadt, Germany; Department of Biology, Technische Universität Darmstadt, Darmstadt, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Wiedemann
authors.affiliation: Department of Biophysics, GSI Helmholtzzentrum für Schwerionenforschung , Darmstadt , Germany.
authors.forename: Joana
authors.initials: J
authors.lastname: Zink
authors.affiliation: Department of Biophysics, GSI Helmholtzzentrum für Schwerionenforschung , Darmstadt , Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Thoennes
authors.affiliation: Department of Biophysics, GSI Helmholtzzentrum für Schwerionenforschung , Darmstadt , Germany.
authors.forename: Maike
authors.initials: M
authors.lastname: Stange
authors.affiliation: Department of Biology, Technische Universität Darmstadt , Darmstadt , Germany.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Layer
authors.affiliation: Department of Dermatology, Darmstadt Hospital , Darmstadt , Germany.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Kovacs
authors.affiliation: Department of Dermatology, Darmstadt Hospital , Darmstadt , Germany.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Podda
authors.affiliation: Department of Biophysics, GSI Helmholtzzentrum für Schwerionenforschung, Darmstadt, Germany; Department of Biology, Technische Universität Darmstadt, Darmstadt, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Durante
authors.affiliation: Department of Biophysics, GSI Helmholtzzentrum für Schwerionenforschung, Darmstadt, Germany; Hochschule Darmstadt, Darmstadt, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Fournier
keywords: apoptosis; carbon ions; differentiation; human skin equivalent; inflammation; ionizing irradiation; keratinocytes; proliferation