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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
Author(s) -
Epperly Michael W.,
Travis Elizabeth L.,
Whitsett Jeffrey A.,
Raineri Ines,
Epstein Charles J.,
Greenberger Joel S.
Publication year - 2001
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/1097-0215(20010220)96:1<11::aid-ijc2>3.0.co;2-r
Subject(s) - sod2 , transgene , genetically modified mouse , biology , superoxide dismutase , pulmonary fibrosis , lung , microbiology and biotechnology , sod1 , cancer research , immunology , medicine , gene , endocrinology , oxidative stress , biochemistry
Intratracheal (IT) injection of the transgene for human manganese superoxide dismutase in plasmid/liposome ( SOD2 ‐PL) complex prior to irradiation protects C57BL/6J mice from whole lung irradiation‐induced organizing alveolitis/fibrosis. Transgene mRNA was detected in alveolar type II (AT‐II) and tracheobronchial 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 would provide intrinsic radioresistance, transgenic mice of two strains were compared with age‐matched controls. Other groups of surfactant promoter‐restricted (SP1)‐ SOD2 transgenic mice or control FeVB/NHsd mice received IT SOD2 ‐PL gene therapy prior to irradiation. There was no significant intrinsic lung protection in either strain of MnSOD transgenic mice. The SP1‐ SOD2 transgenic mice were protected from lung damage by IT injection of the human SOD2 ‐PL complex 24 hours prior to irradiation. Thus, overexpression of either human SOD2 or murine Sod2 in the lungs of transgenic mice does not provide intrinsic lung irradiation protection. The overexpression of SOD2 in the SP1‐ SOD2 mice may have made the mice more sensitive to irradiation. Int. J. Cancer (Radiat. Oncol. Invest.) 96, 11–21 (2001). © 2001 Wiley‐Liss, Inc.