Modulation of gene expression in endothelial cells in response to high LET nickel ion irradiation

Beck,Michaël; Rombouts,Charlotte; Moreels,Marjan; Aerts,An; Quintens,Roel; Tabury,Kevin; Michaux,Arlette; Janssen,Ann; Neefs,Mieke; Ernst,Eric; Dieriks,Birger; Lee,Ryonfa; De Vos,Winnok  H.; Lambert,Charles; Van Oostveldt,Patrick; Baatout,Sarah

doi:10.3892/ijmm.2014.1893

Modulation of gene expression in endothelial cells in response to high LET nickel ion irradiation

Authors:
- Michaël Beck
- Charlotte Rombouts
- Marjan Moreels
- An Aerts
- Roel Quintens
- Kevin Tabury
- Arlette Michaux
- Ann Janssen
- Mieke Neefs
- Eric Ernst
- Birger Dieriks
- Ryonfa Lee
- Winnok H. De Vos
- Charles Lambert
- Patrick Van Oostveldt
- Sarah Baatout
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Affiliations: Laboratory of Radiobiology, Institute for Environment, Health and Safety, Belgian Nuclear Research Centre (SCK‑CEN), Mol, Belgium, Laboratory of Connective Tissues Biology, GIGA-Cancer, University of Liège, Liège, Belgium, Department of Molecular Biotechnology, Ghent University, Ghent, Belgium, Biophysics Department, GSI Helmholtzzentrum für Schwerionenforschung, Darmstadt, Germany
Published online on: August 11, 2014 https://doi.org/10.3892/ijmm.2014.1893
Pages: 1124-1132

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Abstract

Ionizing radiation can elicit harmful effects on the cardiovascular system at high doses. Endothelial cells are critical targets in radiation-induced cardiovascular damage. Astronauts performing a long-term deep space mission are exposed to consistently higher fluences of ionizing radiation that may accumulate to reach high effective doses. In addition, cosmic radiation contains high linear energy transfer (LET) radiation that is known to produce high values of relative biological effectiveness (RBE). The aim of this study was to broaden the understanding of the molecular response to high LET radiation by investigating the changes in gene expression in endothelial cells. For this purpose, a human endothelial cell line (EA.hy926) was irradiated with accelerated nickel ions (Ni) (LET, 183 keV/µm) at doses of 0.5, 2 and 5 Gy. DNA damage was measured 2 and 24 h following irradiation by γ-H2AX foci detection by fluorescence microscopy and gene expression changes were measured by microarrays at 8 and 24 h following irradiation. We found that exposure to accelerated nickel particles induced a persistent DNA damage response up to 24 h after treatment. This was accompanied by a downregulation in the expression of a multitude of genes involved in the regulation of the cell cycle and an upregulation in the expression of genes involved in cell cycle checkpoints. In addition, genes involved in DNA damage response, oxidative stress, apoptosis and cell-cell signaling (cytokines) were found to be upregulated. An in silico analysis of the involved genes suggested that the transcription factors, E2F and nuclear factor (NF)-κB, may be involved in these cellular responses.

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