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17 July 2013 Conditional Radioresistance of tet-Inducible Manganese Superoxide Dismutase Bone Marrow Stromal Cell Lines
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Mitochondrial targeted manganese superoxide dismutase is a major antioxidant enzyme, the levels of which modulate the response of cells, tissues and organs to ionizing irradiation. We developed a Tet-regulated MnSOD mouse (MnSODtet) to examine the detailed relationship between cellular MnSOD concentration and radioresistance and carried out in vitro studies using bone marrow culture derived stromal cell lines (mesenchymal stem cells). Homozygous MnSODtet/tet cells had low levels of MnSOD, reduced viability and proliferation, increased radiosensitivity, elevated overall antioxidant stores, and defects in cell proliferation and DNA strand-break repair. Doxycycline (doxy) treatment of MnSODtet/tet cells increased MnSOD levels and radioresistance from ñ of 2.79 ± 1.04 to 8.69 ± 1.09 (P = 0.0060) and normalized other biologic parameters. In contrast, MnSODtet/tet cells showed minimal difference in baseline and radiation induced mRNA and protein levels of TGF-β, Nrf2 and NF-κB and radiation induced cell cycle arrest was not dependent upon MnSOD level. These novel MnSODtet/tet mouse derived cells should be valuable for elucidating several parameters of the oxidative stress response to ionizing radiation.

Michael W. Epperly, J. Richard Chaillet, Ronny Kalash, Ben Shaffer, Julie Goff, Darcy Franicola, Xichen Zhang, Tracy Dixon, Frank Houghton, Hong Wang, Hebist Berhane, Cynthia Romero, Jee-Hong Kim, and Joel S. Greenberger "Conditional Radioresistance of tet-Inducible Manganese Superoxide Dismutase Bone Marrow Stromal Cell Lines," Radiation Research 180(2), 189-204, (17 July 2013).
Received: 28 August 2012; Accepted: 1 March 2013; Published: 17 July 2013

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