Cell Membrane Oxidative Damage Induced by Gamma-Radiation and Apoptotic Sensitivity

Abstract

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 gamma-irradiation ofliposomal 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 alpha-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.

Radical scavenging activity of extruded corn gruels with addition of linden inflorescence

“…Reactive oxygen species (ROS) have been implicated in many pathological conditions, including rheumatoid arthritis [14], hemorrhagic shock [15], cardiomyopathy [16] and gastrointestinal ischemia [17]. High concentration of ROS leads to destruction of cell membranes, proteins, and nucleic acids, which is dangerous because it may lead to carcinoma formation [18,19].…”

Low energy proton beam induces tumor cell apoptosis through reactive oxygen species and activation of caspases

“…By the γ irradiation, p53, caspase-3 and JNK/SAPK are reported to be associated with cell cycle arrest and apoptosis (Samuni et al, 2005). It is well identified that ROS may be involved in γ irradiation-induced apoptosis of cancer cells as well as normal cells (Mishra, 2004). The activation of p53 is typically induced by DNA damaging stresses, and in ROS-induced apoptosis ROS appears to be generated downstream of p53-induced caspase activation (Ueda et al, 2002).…”

Overcoming the radioresistance of prostate cancer cells with a novel Bcl-2 inhibitor

“…This facilitates the use of radiotherapy at lower doses with higher efficacies. Although the precise molecular mechanism by which radiation triggers apoptotic or clonogenic cell death is not fully understood, the cytoplasmic membrane and DNA are the two major cellular targets (Higuchi, 2003;Mishra, 2004). Damaging these cellular components induces ROS generation and DNA double-strand breaks (DSBs).…”