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Polyamines Protect against Radiation-Induced Oxidative Stress. A.W. von Deutsch1, C.D. Mitchell1,6, I.K. Abukhalaf1,2,3, G. Sanford1,4, K. Dutt1,5, N. Silvestrov2,3, B. Klement1,6 and D.A. von Deutsch1,2,3. 1Space Medicine and Life Sciences Research Ctr, 2Dept. of Pharmacology & Toxicology, 3Clinical Research Ctr, 4Dept. of Biochemistry, Immunology, and Microbiology, 5Dept. of Pathology, 6Dept. of Neurobiology and Anatomy, Morehouse School of Medicine (MSM), 720 Westview Dr, SW, Atlanta, GA 30310, 7MBRS Program, MSM and Morehouse College, Atlanta, GA 30310. 

   One of the hazards associated with working in outer space is radiation. Space radiation can result in direct damage to cells and give rise to free radicals. Radiation-induced free radical generation can subsequently cause extensive damage to cells as well as induce a damage cascade. The purpose of this study was to: 1) characterize the impact of iron and myoglobin on cellular oxidative damage profile and 2) study the role of polyamine pathway in attenuating free radical-induced damage. Methods. Human fetal retinal and endothelial cells were cultured in 6 and 12-well trays with half of the wells receiving treatment and the other receiving vehicle (PBS). Trays were exposed to UV-C for a fixed exposure time of 30 or 60 min to determine the role of polyamines part of the endogenous antioxidant protection against the radiation-induced oxidative stress. The enzyme ornithine decarboxylase (ODC) was stimulated with ornithine (10-7M), the Я2-adrenoceptor agonist clenbuterol (10-7M), or arginine (10-7M). The ODC inhibitor difluoromethylornithine (DFMO, 10-5M) was used to block polyamine synthesis. Xanthine oxidase (XO) activity and glutathione levels were measured. Results. Treatment with 10-7 M clenbuterol, catalase, and SOD significantly increased the rate of cell survival while iron and myoglobin significantly caused an increase the death rate in a dose-dependent fashion. The Я2-adrenoceptor antagonist ICI-118,551 significantly attenuated clenbuterol's protective effect while DFMO completely blocked it. Conclusions. This study confirms that polyamines are neuroprotective and protect cells against oxidative damage. This work was supported, in part, by NASA Grant NCC9-112, NIH Grants 1R25RR17694, 5P20RR011104, and MBRS Grant 506GM08248.