Journal Article

Increased effectiveness of carbon ions in the production of reactive oxygen species in normal human fibroblasts

Till Dettmering, Sebastian Zahnreich, Miriam Colindres-Rojas, Marco Durante, Gisela Taucher-Scholz and Claudia Fournier

in Journal of Radiation Research

Volume 56, issue 1, pages 67-76
Published in print January 2015 | ISSN: 0449-3060
Published online October 2014 | e-ISSN: 1349-9157 | DOI: https://dx.doi.org/10.1093/jrr/rru083

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  • Clinical Genetics
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  • Epidemiology
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  • Nuclear Chemistry, Photochemistry, and Radiation

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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.

Keywords: oxidative stress; high-LET; fibroblasts; reactive oxygen species; growth arrest; genomic instability

Journal Article.  5369 words.  Illustrated.

Subjects: Clinical Genetics ; Molecular Biology and Genetics ; Epidemiology ; Radiology ; Nuclear Chemistry, Photochemistry, and Radiation

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