Overexpression of manganese superoxide dismutase (MnSOD) in whole lung or alveolar type II cells of MnSOD transgenic mice does not provide intrinsic lung irradiation protection

Intratracheal (IT) injection of the transgene for human manganese superoxid e dismutase in plasmid/liposome (SOD2-PL) complex prior to irradiation prot ects C57BL/6J mice from whole lung irradiation-induced organizing alveoliti s/fibrosis. Transgene mRNA was detected in alveolar type II (AT-II) and tra cheobronchial tree cells explanted to culture 48 hours after gene therapy. To determine whether constitutive overexpression of murine MnSOD (Sod2) in whole lung or surfactant promoter-restricted AT-II cells (SP1)-SOD2 mice wo uld provide intrinsic radioresistance, transgenic mice of two strains were compared with age-matched controls. Other groups of surfactant promoter-res tricted (SP1)-SOD2 transgenic mice or control FeVB/NHsd mice received IT SO D2-PL gene therapy prior to irradiation. There was no significant intrinsic lung protection in either strain of MnSOD transgenic mice. The SP1-SOD2 tr ansgenic mice were protected from lung damage by IT injection of the human SOD2-PL complex 24 hours prior to irradiation. Thus, overexpression of eith er human SOD2 or murine Sod2 in the lungs of transgenic mice does not provi de intrinsic lung irradiation protection. The overexpression of SOD2 in the SP1-SOD2 mice may have made the mice more sensitive to irradiation. (C) 20 01 Wiley-Liss, Inc.