title: Increased effectiveness of carbon ions in the production of reactive oxygen species in normal human fibroblasts.
abstract: The production of reactive oxygen species (ROS), especially superoxide anions (O2 (·-)), is enhanced in many normal and tumor cell types in response to ionizing radiation. The influence of ionizing radiation on the regulation of ROS production is considered as an important factor in the long-term effects of irradiation (such as genomic instability) that might contribute to the development of secondary cancers. In view of the increasing application of carbon ions in radiation therapy, we aimed to study the potential impact of ionizing density on the intracellular production of ROS, comparing photons (X-rays) with carbon ions. For this purpose, we used normal human cells as a model for irradiated tissue surrounding a tumor. By quantifying the oxidization of Dihydroethidium (DHE), a fluorescent probe sensitive to superoxide anions, we assessed the intracellular ROS status after radiation exposure in normal human fibroblasts, which do not show radiation-induced chromosomal instability. After 3-5 days post exposure to X-rays and carbon ions, the level of ROS increased to a maximum that was dose dependent. The maximum ROS level reached after irradiation was specific for the fibroblast type. However, carbon ions induced this maximum level at a lower dose compared with X-rays. Within ∼1 week, ROS decreased to control levels. The time-course of decreasing ROS coincides with an increase in cell number and decreasing p21 protein levels, indicating a release from radiation-induced growth arrest. Interestingly, radiation did not act as a trigger for chronically enhanced levels of ROS months after radiation exposure.
authors.affiliation: GSI Helmholtz Centre for Heavy Ion Research, Biophysics, Planckstraße 1, 64291 Darmstadt, Germany.
authors.forename: Till
authors.initials: T
authors.lastname: Dettmering
authors.affiliation: GSI Helmholtz Centre for Heavy Ion Research, Biophysics, Planckstraße 1, 64291 Darmstadt, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Zahnreich
authors.affiliation: GSI Helmholtz Centre for Heavy Ion Research, Biophysics, Planckstraße 1, 64291 Darmstadt, Germany.
authors.forename: Miriam
authors.initials: M
authors.lastname: Colindres-Rojas
authors.affiliation: GSI Helmholtz Centre for Heavy Ion Research, Biophysics, Planckstraße 1, 64291 Darmstadt, Germany TU Darmstadt, Institute for Condensed Matter Physics, Hochschulstraße 6-8, 64289 Darmstadt, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Durante
authors.affiliation: GSI Helmholtz Centre for Heavy Ion Research, Biophysics, Planckstraße 1, 64291 Darmstadt, Germany.
authors.forename: Gisela
authors.initials: G
authors.lastname: Taucher-Scholz
authors.affiliation: GSI Helmholtz Centre for Heavy Ion Research, Biophysics, Planckstraße 1, 64291 Darmstadt, Germany c.fournier@gsi.de.
authors.forename: Claudia
authors.initials: C
authors.lastname: Fournier
mesh_terms: D002247:Carbon Isotopes; D002460:Cell Line; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D004307:Dose-Response Relationship, Radiation; D005347:Fibroblasts / Q000378:metabolism* / Q000528:radiation effects*; D020450:Heavy Ions; D006801:Humans; D007231:Infant, Newborn; D011829:Radiation Dosage; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology* / Q000528:radiation effects
chemical_list: C493956:CDKN1A protein, human; D002247:Carbon Isotopes; D050759:Cyclin-Dependent Kinase Inhibitor p21; D017382:Reactive Oxygen Species
keywords: fibroblasts; genomic instability; growth arrest; high-LET; oxidative stress; reactive oxygen species