EFFICACY OF MEMBRANE SEALING THERAPY IN RADIATION INJURY

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Numerous studies have produced results which indicate that the cell membrane is an important site of cell damage from ionizing irradiation. The cell membranes are a major target for radiation induced free radicals. Development of effective therapeutic strategies to treat ionizing radiation injuries ("radiation burns") continues to be an important medical research objective. Most radioprotectant strategies are based on free radical scavengers which are effective if administered before the exposure. We have found that poloxamer 188, a biocompatible non-ionic surfactant, applied ten minutes after radiation exposure induces sealing of membranes permeabilized by intense gamma irradiation (appendix I). In addition, we have demonstrated that poloxaner 188 and similar molecules, are capable of sealing electroporated and thermally permeabilized cell plasma membranes, resulting in restoration of cell viability (appendices ll & III). We propose to quantify the dose response relationship between gamma irradiation exposure and altered plasma membrane transport properties; determine the efficacy of selected surfactant agents on membrane and viability after irradiation of isolated adult skeletal muscle fibers; investigate the effects of isolated irradiation membrane sealing on the kinetics of apoptosis and necrosis in proliferating cells; and examine the therapeutic efficacy of these surfactants for prevention of skeletal muscle necrosis in situ. The major goals of this project are to quantitatively describe the effect of irradiation on plasma membrane transport properties and determine if surfactant based cell membrane repair strategies can be effective in preventing tissue necrosis following toxic level exposure to ionizing irradiation.