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.
Highlights
Carbon ions are successfully being used in radiotherapy to inactivate tumors that are untreatable with classical methods using photons [1, 2]
Oxidative stress is manifested as an increase in the production of reactive oxygen species (ROS), which arise from a range of cellular sources [4]: a large fraction come from mitochondria in the form of superoxide anions (O2·–) as a normal physiological process [5]
The ROS levels plotted in the response curve correspond to the maximum fluorescence intensity values, which were obtained between days 3 and 5 after exposure
Summary
Carbon ions are successfully being used in radiotherapy to inactivate tumors that are untreatable with classical methods using photons [1, 2]. In general, more effective than photons in inactivating tumors as a result of higher ionization density, and the surrounding normal tissue is better spared than when using photon irradiation as a result of their inverted depth–dose profile [2]. An improved understanding of the physiological consequences of exposure to carbon ions is required, in particular with respect to effects evoked in normal tissue located within the irradiation field. Oxidative stress is manifested as an increase in the production of reactive oxygen species (ROS), which arise from a range of cellular sources [4]: a large fraction come from mitochondria in the form of superoxide anions (O2·–) as a normal physiological process [5]. A perturbation of this balance in normal human tissue can result in increased ROS levels and oxidative stress
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