Radioprotection of lung and esophagus by overexpression of the human manganese superoxide dismutase transgene.

Protection of normal tissue from radiation-induced damage has been demonstrated in the murine lung and esophagus using human manganese superoxide dismutase (MnSOD) plasmid/liposome complex (PL). C57BL/6J mice were injected intratracheally with MnSOD-PL, LacZ-PL, or metallothionein (MT2)-PL and irradiated 24 hours later at 2,000 cGy to the pulmonary cavity. Mice injected with MnSOD-PL had significantly increased survival compared with control, LacZ-PL, or MT2-PL irradiated mice. In an esophagitis model, male C3H/HeJ mice were injected intraesophageally with either MnSOD-PL or LacZ-PL and irradiated 24 hours later at 3,500 cGy to the pulmonary cavity. Mice injected with MnSOD-PL had significantly increased survival after irradiation at 3,500 cGy compared with control or LacZ-PL injected mice. However, orthotopic 3LL lung tumors in C57BL/6J mice were not protected from radiation following injection of MnSOD-PL, as seen by increased survival of mice with these tumors following irradiation. MnSOD-PL gene therapy protected normal lung and esophagus but not 3LL orthotopic lung tumors from radiation-induced damage.