title: Fate of D3 mouse embryonic stem cells exposed to X-rays or carbon ions.
abstract: The risk of radiation exposure during embryonic development is still a major problem in radiotoxicology. In this study we investigated the response of the murine embryonic stem cell (mESC) line D3 to two radiation qualities: sparsely ionizing X-rays and densely ionizing carbon ions. We analyzed clonogenic cell survival, proliferation, induction of chromosome aberrations as well as the capability of cells to differentiate to beating cardiomyocytes up to 3 days after exposure. Our results show that, for all endpoints investigated, carbon ions are more effective than X-rays at the same radiation dose. Additionally, in long term studies (≥8 days post-irradiation) chromosomal damage and the pluripotency state were investigated. These studies reveal that pluripotency markers are present in the progeny of cells surviving the exposure to both radiation types. However, only in the progeny of X-ray exposed cells the aberration frequency was comparable to that of the control population, while the progeny of carbon ion irradiated cells harbored significantly more aberrations than the control, generally translocations. We conclude that cells surviving the radiation exposure maintain pluripotency but may carry stable chromosomal rearrangements after densely ionizing radiation.
authors.affiliation: Biophysics Department, GSI Helmholtz Centre for Heavy Ion Research, Planckstraße 1, 64291 Darmstadt, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Luft
authors.affiliation: Biophysics Department, GSI Helmholtz Centre for Heavy Ion Research, Planckstraße 1, 64291 Darmstadt, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Pignalosa
authors.affiliation: Biophysics Department, GSI Helmholtz Centre for Heavy Ion Research, Planckstraße 1, 64291 Darmstadt, Germany; Laboratory of Radiation Biology, Joint Institute for Nuclear Research, Joliot-Curie 6, 141980 Dubna, Moscow Region, Russia.
authors.forename: E
authors.initials: E
authors.lastname: Nasonova
authors.affiliation: Biophysics Department, GSI Helmholtz Centre for Heavy Ion Research, Planckstraße 1, 64291 Darmstadt, Germany.
authors.forename: O
authors.initials: O
authors.lastname: Arrizabalaga
authors.affiliation: Biophysics Department, GSI Helmholtz Centre for Heavy Ion Research, Planckstraße 1, 64291 Darmstadt, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Helm
authors.affiliation: Biophysics Department, GSI Helmholtz Centre for Heavy Ion Research, Planckstraße 1, 64291 Darmstadt, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Durante
authors.affiliation: Biophysics Department, GSI Helmholtz Centre for Heavy Ion Research, Planckstraße 1, 64291 Darmstadt, Germany. Electronic address: s.ritter@gsi.de.
authors.forename: S
authors.initials: S
authors.lastname: Ritter
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002244:Carbon; D002454:Cell Differentiation / Q000528:radiation effects; D002460:Cell Line; D002470:Cell Survival / Q000528:radiation effects; D002869:Chromosome Aberrations / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects*; D005434:Flow Cytometry; D059565:G2 Phase Cell Cycle Checkpoints / Q000528:radiation effects; D020450:Heavy Ions; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects*; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D013997:Time Factors; D014965:X-Rays
chemical_list: D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D002244:Carbon
keywords: Carbon ions; Cardiomyocyte formation; Chromosome aberrations; Embryonic stem cells; Ionizing radiation; Pluripotency