RT Journal Article ID 70e477925da5b459 A1 Mishra, Kaushala Prasad T1 Cell Membrane Oxidative Damage Induced by Gamma-Radiation and Apoptotic Sensitivity JF Journal of Environmental Pathology, Toxicology and Oncology JO JEP(T) YR 2004 FD 2004-05-10 VO 23 IS 1 OP 6 AB Ionizing radiation-generated reactive oxygen species (ROS) resulting in oxidative damage to the cell membrane and its consequent role in the mechanism of apoptotic cell death have been receiving growing attention in cellular radiobiology. In recent years, evidence has accumulated to suggest that it is the damage to the cell membrane that contributes to the radiation cell killing. It has been demonstrated that degradation of membrane-bound sphingomyelinase (SMase) after irradiation of bovine endothelial cell produces ceramide, which initiates an apoptotic cascade, suggesting membrane-triggered events in the mechanism of cellular apoptosis. Fluorescence and electron spin resonance (ESR) studies from γ-irradiation of liposomal vesicles have shown that radiation-mediated lipid damage was modified by the inclusion of structure-modulating agents (e.g., cholesterol) and antioxidants (e.g., tocopherol, eugenol). The magnitude of the modification of the damage was found to be dependent on the concentration of these modifiers. Moreover, experiments on dipalmitoyl phosphatidyl choline (DPPC) unilamellar liposomes demonstrated a biphasic behavior of radiation damage, which was remarkably modified by ascorbic acid and α-tocopherol in a concentration-dependent fashion. The comparison of their protective effects showed that ascorbic acid was less effective than tocopherol against radiation damage to liposomes. Studies on irradiated mouse thymocytes employing FDA fluorescence probe have suggested post-irradiation time- and dose-dependent changes in membrane permeability. The determination of induction of apoptosis in irradiated thymocytes showed a time-dependent DNA fragmentation, suggesting that radiation-induced permeability changes and occurrence of apoptotic death in thymocytes were closely correlated. These results are discussed, with an emphasis on membrane-damage-mediated apoptotic death with relevance to improvement of cancer radiotherapy. PB Begell House LK https://www.dl.begellhouse.com/journals/0ff459a57a4c08d0,72780bba1bf964e3,70e477925da5b459.html