Overexpression of the MnSOD transgene product protects cryopreserved bone marrow hematopoietic progenitor cells from ionizing radiation.
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.
Epperly
Michael W
MW
Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15213, USA. epperly@pitt.edu
Epperly
Laura D
LD
Niu
YunYun
Y
Wang
Hong
H
Zhang
Xichen
X
Franicola
Darcy
D
Greenberger
Joel S
JS
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology* / Q000528:radiation effects*; D002478:Cells, Cultured; D015925:Cryopreservation / Q000379:methods*; D019610:Cytoprotection / Q000502:physiology / Q000528:radiation effects; D005260:Female; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology* / Q000528:radiation effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D011839:Radiation, Ionizing; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D014162:Transfection / Q000379:methods; D019076:Transgenes / Q000502:physiology; D015854:Up-Regulation / Q000502:physiology
D013482:Superoxide Dismutase