Fate of D3 mouse embryonic stem cells exposed to X-rays or carbon ions

Mutat Res Genet Toxicol Environ Mutagen. 2014 Jan 15:760:56-63. doi: 10.1016/j.mrgentox.2013.12.004. Epub 2014 Jan 5.

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.

Keywords: Carbon ions; Cardiomyocyte formation; Chromosome aberrations; Embryonic stem cells; Ionizing radiation; Pluripotency.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Carbon*
  • Cell Differentiation / radiation effects
  • Cell Line
  • Cell Survival / radiation effects
  • Chromosome Aberrations / radiation effects
  • Dose-Response Relationship, Radiation
  • Embryonic Stem Cells / cytology
  • Embryonic Stem Cells / metabolism
  • Embryonic Stem Cells / radiation effects*
  • Flow Cytometry
  • G2 Phase Cell Cycle Checkpoints / radiation effects
  • Heavy Ions*
  • In Situ Hybridization, Fluorescence
  • Mice
  • Myocytes, Cardiac / cytology
  • Myocytes, Cardiac / metabolism
  • Myocytes, Cardiac / radiation effects
  • Octamer Transcription Factor-3 / metabolism
  • Pluripotent Stem Cells / cytology
  • Pluripotent Stem Cells / metabolism
  • Pluripotent Stem Cells / radiation effects*
  • SOXB1 Transcription Factors / metabolism
  • Time Factors
  • X-Rays

Substances

  • Octamer Transcription Factor-3
  • POU5F1 protein, human
  • SOX2 protein, human
  • SOXB1 Transcription Factors
  • Carbon