Overexpression of the MnSOD Transgene Product Protects Cryopreserved Bone Marrow Hematopoietic Progenitor Cells from Ionizing Radiation

Abstract

We determined whether manganese superoxide dismutase (MnSOD)-plasmid liposome (PL) transfection of C57BL/ 6NHsd mouse bone marrow protected cells irradiated at room temperature (24 degrees C) or in the cryopreserved state. MnSOD-overexpressing hematopoietic progenitor 2C6 cells were radioresistant compared to the parent 32D cl 3 cells when irradiated frozen or at 24 degrees C. Fresh whole marrow from mice injected intravenously with MnSOD-PL prior to explant as well as explanted marrow single cell suspensions transfected in vitro were irradiated at 24 degrees C or -80 degrees C. In vivo or in vitro transfection of marrow with MnSOD-PL produced significant radiation protection of irradiated marrow progenitor cells compared to controls at 24 degrees C or -80 degrees C. (in vivo transfection D(0) 2.19 +/- 0.21 at 24 degrees C, D(0) 2.10 +/- 0.07 at -80 degrees C compared to control D(0) 1.56 +/- 0.06 or 1.66 +/- 0.04, P = 0.047 and 0.017 respectively; in vitro transfection D(0) 2.35 +/- 0.11 at 24 degrees C, D(0) 3.42 +/- 0.13 at -80 degrees C compared to D(0) 1.81 +/- 0.01 or 2.53 +/- 0.05, P = 0.0087 and 0.0026, respectively). Thus the MnSOD transgene product protects frozen marrow cells as well as marrow cells irradiated at 24 degrees C.