1. ¹Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA
2. ²Department of Molecular Genetics and Microbiology, State University of New York at Stonybrook, Stonybrook, NY, USA

Correspondence: JS Greenberger, Department of Radiation Oncology, University of Pittsburgh Cancer Institute, B346-PUH, 200 Lothrop Street, Pittsburgh, PA 152 13, USA

Received 11 April 2002; Accepted 23 June 2002.

Abstract

Intratracheal (IT) injection of manganese superoxide dismutase–plasmid/liposome (MnSOD-PL) complexes prior to whole lung irradiation of C57BL/6J mice provides significant protection from acute and chronic irradiation damage. We determined the duration of increased MnSOD biochemical activity and differential expression of a hemagglutinin (HA) epitope-tagged MnSOD transgene. HA–MnSOD–PL was IT injected at doses of 0–1000 g, and mice were killed 1,2,3 or 4 days later. Other groups of mice were irradiated to 20 Gy to the pulmonary cavity 24 h after injection and killed at the same time points as non-irradiated mice. Both non-irradiated and irradiated groups of mice showed increased MnSOD biochemical activity with plasmid dose that plateaued at 100 g of MnSOD plasmid DNA. In control mice, MnSOD biochemical activity decreased at 2, 3 or 4 days after injection. In irradiated mice, MnSOD biochemical activity decreased at day 2 but increased on days 3 and 4. HA–MnSOD expression decreased in broncheoalveolar macrophages and alveolar type-II cells 3 days after injection in non-irradiated and irradiated mice, but remained elevated in endothelial and epithelial cells past 4 days. The data provide a rationale for every second-day administration of intrapulmonary MnSOD–PL in clinical trials of radioprotective gene therapy. This should be sufficient to provide radioprotection during radiation treatments.