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- Title
941. Manganese Superoxide Dismutase-Plasmid Liposome (MnSOD-PL) Transgenic Effects on Irradiation-Induced Reactive Oxygen Species (ROS) in Normal Tissue Also Destabilize Antioxidant Pools in Orthotopic Oral Cavity Tumors.
- Authors
Epperly, Michael W.; Suhua Nie; Kanai, Anthony J.; Greenberger, Joel S.
- Abstract
Overexpression of MnSOD has been demonstrated to sensitize tumor cells to irradiation. To determine the mechanism, we injected SCC-VII murine squamous cell carcinoma cells into the cheeks of C3H/HeNsd mice. Seven days later, the mice were injected eitherintravenously (I.V.) or intraorally (I.O.) with MnSOD-PL (100 μg plasmid DNA). Twenty-four hours later, the mice were irradiated to 18 Gy to both tumor and oral cavity. The mice were sacrificed 15 minutes later, tumor and normal oral mucosa excised, frozen in liquid nitrogen, and stored in a −80° freezer. Total protein thiols as well as total glutathione were measured. We also measured the production of nitric oxide and peroxynitrite utilizing small electroprobes in tissues in situ. Following irradiation oral mucosa showed no detectable changes in total protein thiols if mice were injected with MnSOD- PL I.V. or I.O. There were no significant changes in total protein thiols or GSH from tumors of irradiated control mice or mice injected with MnSOD-PL I.O. However, irradiated SCC-VII tumors from mice injected with MnSOD-PL I.V. showed decreased total protein thiols and GSH compared to tumors from control mice (p = 0.0008 or 0.0103, respectively). Measurements of reactive oxygen species (ROS) in SCC-VII cells in vivo following irradiation revealed increased nitric oxide production accompanied by increased peroxynitrite and superoxide production. SCC-VII tumors in mice administered MnSOD-PL I.V. showed no irradiation-induced increase in superoxide or peroxynitrite production. Overexpression of MnSOD- PL in orthotopic squamous oral tumors sensitizes to irradiation by increased hydrogen peroxide production, from the conversion of superoxide to H2O2, and reduces antioxidant levels in tumor tissue. Thus, MnSOD-PL I.V. administration may be radioprotective for normal tissue while radiosensitizing tumors in the same field by altering antioxidant levels in the tumors.Molecular Therapy (2006) 13, S363–S363; doi: 10.1016/j.ymthe.2006.08.1032
- Subjects
ORAL cancer; GENE expression; LIPOSOMES; CANCER cells; REACTIVE oxygen species; ANTIOXIDANTS
- Publication
Molecular Therapy, 2006, Vol 13, pS363
- ISSN
1525-0016
- Publication type
Article
- DOI
10.1016/j.ymthe.2006.08.1032