title: Modulation of gene expression in endothelial cells in response to high LET nickel ion irradiation.
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.
authors.affiliation: Laboratory of Radiobiology, Institute for Environment, Health and Safety, Belgian Nuclear Research Centre (SCK‑CEN), Mol, Belgium.
authors.forename: Michaël
authors.initials: M
authors.lastname: Beck
authors.affiliation: Laboratory of Radiobiology, Institute for Environment, Health and Safety, Belgian Nuclear Research Centre (SCK‑CEN), Mol, Belgium.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Rombouts
authors.affiliation: Laboratory of Radiobiology, Institute for Environment, Health and Safety, Belgian Nuclear Research Centre (SCK‑CEN), Mol, Belgium.
authors.forename: Marjan
authors.initials: M
authors.lastname: Moreels
authors.affiliation: Laboratory of Radiobiology, Institute for Environment, Health and Safety, Belgian Nuclear Research Centre (SCK‑CEN), Mol, Belgium.
authors.forename: An
authors.initials: A
authors.lastname: Aerts
authors.affiliation: Laboratory of Radiobiology, Institute for Environment, Health and Safety, Belgian Nuclear Research Centre (SCK‑CEN), Mol, Belgium.
authors.forename: Roel
authors.initials: R
authors.lastname: Quintens
authors.affiliation: Laboratory of Radiobiology, Institute for Environment, Health and Safety, Belgian Nuclear Research Centre (SCK‑CEN), Mol, Belgium.
authors.forename: Kevin
authors.initials: K
authors.lastname: Tabury
authors.affiliation: Laboratory of Radiobiology, Institute for Environment, Health and Safety, Belgian Nuclear Research Centre (SCK‑CEN), Mol, Belgium.
authors.forename: Arlette
authors.initials: A
authors.lastname: Michaux
authors.affiliation: Laboratory of Radiobiology, Institute for Environment, Health and Safety, Belgian Nuclear Research Centre (SCK‑CEN), Mol, Belgium.
authors.forename: Ann
authors.initials: A
authors.lastname: Janssen
authors.affiliation: Laboratory of Radiobiology, Institute for Environment, Health and Safety, Belgian Nuclear Research Centre (SCK‑CEN), Mol, Belgium.
authors.forename: Mieke
authors.initials: M
authors.lastname: Neefs
authors.affiliation: Laboratory of Connective Tissues Biology, GIGA-Cancer, University of Liège, Liège, Belgium.
authors.forename: Eric
authors.initials: E
authors.lastname: Ernst
authors.affiliation: Department of Molecular Biotechnology, Ghent University, Ghent, Belgium.
authors.forename: Birger
authors.initials: B
authors.lastname: Dieriks
authors.affiliation: Biophysics Department, GSI Helmholtzzentrum für Schwerionenforschung, Darmstadt, Germany.
authors.forename: Ryonfa
authors.initials: R
authors.lastname: Lee
authors.affiliation: Department of Molecular Biotechnology, Ghent University, Ghent, Belgium.
authors.forename: Winnok H
authors.initials: WH
authors.lastname: De Vos
authors.affiliation: Laboratory of Connective Tissues Biology, GIGA-Cancer, University of Liège, Liège, Belgium.
authors.forename: Charles
authors.initials: C
authors.lastname: Lambert
authors.affiliation: Department of Molecular Biotechnology, Ghent University, Ghent, Belgium.
authors.forename: Patrick
authors.initials: P
authors.lastname: Van Oostveldt
authors.affiliation: Laboratory of Radiobiology, Institute for Environment, Health and Safety, Belgian Nuclear Research Centre (SCK‑CEN), Mol, Belgium.
authors.forename: Sarah
authors.initials: S
authors.lastname: Baatout
mesh_terms: D001665:Binding Sites; D004249:DNA Damage; D015536:Down-Regulation / Q000235:genetics; D042783:Endothelial Cells / Q000378:metabolism / Q000528:radiation effects*; D020869:Gene Expression Profiling; D006657:Histones / Q000378:metabolism; D006801:Humans; D007477:Ions; D018499:Linear Energy Transfer; D009532:Nickel / Q000737:chemistry*; D011839:Radiation, Ionizing; D014157:Transcription Factors / Q000378:metabolism; D015854:Up-Regulation / Q000528:radiation effects
chemical_list: C468783:H2AX protein, human; D006657:Histones; D007477:Ions; D014157:Transcription Factors; D009532:Nickel