title: Higher Initial DNA Damage and Persistent Cell Cycle Arrest after Carbon Ion Irradiation Compared to X-irradiation in Prostate and Colon Cancer Cells.
abstract: The use of charged-particle beams, such as carbon ions, is becoming a more and more attractive treatment option for cancer therapy. Given the precise absorbed dose-localization and an increased biological effectiveness, this form of therapy is much more advantageous compared to conventional radiotherapy, and is currently being used for treatment of specific cancer types. The high ballistic accuracy of particle beams deposits the maximal dose to the tumor, while damage to the surrounding healthy tissue is limited. In order to better understand the underlying mechanisms responsible for the increased biological effectiveness, we investigated the DNA damage and repair kinetics and cell cycle progression in two p53 mutant cell lines, more specifically a prostate (PC3) and colon (Caco-2) cancer cell line, after exposure to different radiation qualities. Cells were irradiated with various absorbed doses (0, 0.5, and 2 Gy) of accelerated (13)C-ions at the Grand Accélérateur National d'Ions Lourds facility (Caen, France) or with X-rays (0, 0.1, 0.5, 1, 2, and 5 Gy). Microscopic analysis of DNA double-strand breaks showed dose-dependent increases in γ-H2AX foci numbers and foci occupancy after exposure to both types of irradiation, in both cell lines. However, 24 h after exposure, residual damage was more pronounced after lower doses of carbon ion irradiation compared to X-irradiation. Flow cytometric analysis showed that carbon ion irradiation induced a permanent G2/M arrest in PC3 cells at lower doses (2 Gy) compared to X-rays (5 Gy), while in Caco-2 cells the G2/M arrest was transient after irradiation with X-rays (2 and 5 Gy) but persistent after exposure to carbon ions (2 Gy).
authors.affiliation: Expert Group for Molecular and Cellular Biology, Radiobiology Unit, Belgian Nuclear Research Centre (SCK•CEN), Institute for Environment, Health and Safety, Mol, Belgium; Radiation Oncology Department, Center for Molecular Imaging, Radiotherapy and Oncology, Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain (UCL), Bruxelles, Belgium.
authors.forename: Annelies
authors.initials: A
authors.lastname: Suetens
authors.affiliation: Expert Group for Molecular and Cellular Biology, Radiobiology Unit, Belgian Nuclear Research Centre (SCK•CEN), Institute for Environment, Health and Safety, Mol, Belgium; Laboratory of Experimental Radiotherapy, Department of Oncology, KU Leuven, Leuven, Belgium.
authors.forename: Katrien
authors.initials: K
authors.lastname: Konings
authors.affiliation: Expert Group for Molecular and Cellular Biology, Radiobiology Unit, Belgian Nuclear Research Centre (SCK•CEN), Institute for Environment, Health and Safety , Mol , Belgium.
authors.forename: Marjan
authors.initials: M
authors.lastname: Moreels
authors.affiliation: Expert Group for Molecular and Cellular Biology, Radiobiology Unit, Belgian Nuclear Research Centre (SCK•CEN), Institute for Environment, Health and Safety , Mol , Belgium.
authors.forename: Roel
authors.initials: R
authors.lastname: Quintens
authors.affiliation: Expert Group for Molecular and Cellular Biology, Radiobiology Unit, Belgian Nuclear Research Centre (SCK•CEN), Institute for Environment, Health and Safety , Mol , Belgium.
authors.forename: Mieke
authors.initials: M
authors.lastname: Verslegers
authors.affiliation: Expert Group for Molecular and Cellular Biology, Radiobiology Unit, Belgian Nuclear Research Centre (SCK•CEN), Institute for Environment, Health and Safety , Mol , Belgium.
authors.forename: Els
authors.initials: E
authors.lastname: Soors
authors.affiliation: Expert Group for Molecular and Cellular Biology, Radiobiology Unit, Belgian Nuclear Research Centre (SCK•CEN), Institute for Environment, Health and Safety , Mol , Belgium.
authors.forename: Kevin
authors.initials: K
authors.lastname: Tabury
authors.affiliation: Radiation Oncology Department, Center for Molecular Imaging, Radiotherapy and Oncology, Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain (UCL) , Bruxelles , Belgium.
authors.forename: Vincent
authors.initials: V
authors.lastname: Grégoire
authors.affiliation: Expert Group for Molecular and Cellular Biology, Radiobiology Unit, Belgian Nuclear Research Centre (SCK•CEN), Institute for Environment, Health and Safety , Mol , Belgium.
authors.forename: Sarah
authors.initials: S
authors.lastname: Baatout
keywords: Caco-2; DNA double-strand break damage and repair; PC3; carbon ion irradiation; cell cycle progression