Research Project
9619868
The toxicity of ionizing radiation (IR) in diverse cell-types is associated with a high susceptibility of the proteome to oxidative modification. Proteome protection as a tactic for IR survival was recently applied to mice using a synthetic Mn-peptide antioxidant complex (MDP) that specifically prevents protein oxidation and preserves the activity of irradiated enzymes, including those for cellular DNA repair. MDP, adapted from the radioresistant bacterium Deinococcus radiodurans , is nontoxic and protects mice from acute radiation syndromes (ARS). When administered pre- and post-irradiation, all the mice treated with MDP survived 9.5 Gy (LD70/30). MDP diminished ARS and increased serum levels of IL-3, G-CSF and GM-CSF. The radioprotective efficacy of MDP administered to mice post-irradiation, however, remains untested. Note, there is good reason to think that post-exposure treatment alone with MDP will be radioprotective: MDP protects human Jurkat T-cells exposed to 100 Gy when administered 4 hours post-irradiation. We propose to determine whether MDP could serve as an IR countermeasure when administered starting 24, 48, or 72 hours after exposure to x-ray irradiation. The MDP complex will be tested in a standard mouse model for total body irradiation induced ARS (controlled for age and diet), focusing on tissue- and immunological-functions among the survivors.
