Intratracheal injection of manganese superoxide dismutase-plasmid/liposome (Mnsod-pl) Protects normal lung but not orthotopic thoracic tumors from irradiation

Major complications following total body irradiation (TBI) prior to bone marrow transplantation (BMT) include pneumonitis and lung fibrosis. Our laboratory previously demonstrated that intratracheal (IT) injection of C57BL/6J mice with MnSOD-PL complex 24 hours before irradiation reduces organizing alveolitis/fibrosis and increases survival. To demonstrate that overexpression of the human MnSOD transgene in the lung would not protect lung tumors, C57BL/6J mice were injected at the carina with 5×105 orthotopic 3LL Lewis lung carcinoma cells 10 days before MnSOD-PL injection, and sacrificed 24 hrs later. Lungs were removed, orthotopic tumor isolated, RNA extracted, and nested RT-PCR performed with primers specific for the human MnSOD transgene. Expression of the human MnSOD transgene was detected in lung cells but not in orthotopic tumors. Tumor bearing mice that received MnSOD-PL + 1800 cGy showed a significant increase in survival compared to LacZ-PL + 1800 cGy or 1800 cGy alone. Pulmonary MnSOD-PL treatment may compliment TBI by not only protecting the lungs from irradiation but also by increasing tumor control.