Intravenous Injection of Manganese Superoxide Dismutase Plasmid/Liposome Complexes (MnSOD-PL) Protects the Bone Marrow from Irradiation Damage.

Radioprotection of tissues including lung, esophagus, oral cavity and bladder has been demonstrated by local administration of MnSOD-PL. One potential use of the MnSOD-PL is protection of bone marrow as well as other tissues against total body irradiation (TBI) perhaps applicable for first responders who enter areas of high irradiation. To determine if systemically delivered MnSOD-PL protects bone marrow from TBI, groups of C57BL/6NHsd mice were injected intravenously with MnSOD-PL (100 μg of plasmid DNA in 100 ul volume) and irradiated 24 hrs later to 9, 9.5 or 9.75 Gy whole body irradiation. The mice were followed for bone marrow failure. Mice injected with MnSOD-PL showed improved survival at all irradiation doses. After 9 Gy TBI, 93% of the mice injected with MnSOD-PL survived past day 30 compared to 80% of control irradiated mice. At 9.5 Gy, 87% of the MnSOD-PL treated survived past day 30 compared to 53% of control irradiated mice (p = 0.0402). Following 9.75 Gy, the control irradiated mice had a median survival of 16 days with 12.5% survival at 30 days compared to 75% of the MnSOD-PL treated mice (p = 0.0016). To determine the efficiency of marrow transfection mice were injected with a plasmid containing the HA (hemagglutinin) epitoped tagged MnSOD transgene. The marrow was harvested 24 hr later, cytospun, and immunohistochemically stained for HA. The bone marrow demonstrated that 22.1 ± 3.7% of the bone marrow cells expressed HA-MnSOD protein. The results demonstrate that systemically delivered MnSOD-PL protects against TBI induced murine bone marrow damage and improves survival.