| First Author | Epperly MW | Year | 2013 |
| Journal | Radiat Res | Volume | 180 |
| Issue | 2 | Pages | 189-204 |
| PubMed ID | 23862693 | Mgi Jnum | J:209713 |
| Mgi Id | MGI:5568584 | Doi | 10.1667/RR3177.1 |
| Citation | Epperly MW, et al. (2013) Conditional radioresistance of Tet-inducible manganese superoxide dismutase bone marrow stromal cell lines. Radiat Res 180(2):189-204 |
| abstractText | 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 (MnSOD(tet)) 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 MnSOD(tet/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 MnSOD(tet/tet) cells increased MnSOD levels and radioresistance from n of 2.79 +/- 1.04 to 8.69 +/- 1.09 (P = 0.0060) and normalized other biologic parameters. In contrast, MnSOD(tet/tet) cells showed minimal difference in baseline and radiation induced mRNA and protein levels of TGF-beta, Nrf2 and NF-kappaB and radiation induced cell cycle arrest was not dependent upon MnSOD level. These novel MnSOD(tet/tet) mouse derived cells should be valuable for elucidating several parameters of the oxidative stress response to ionizing radiation. |
