TY - JOUR
T1 - 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
AU - Epperly, Michael W.
AU - Travis, Elizabeth L.
AU - Whitsett, Jeffrey A.
AU - Raineri, Ines
AU - Epstein, Charles J.
AU - Greenberger, Joel S.
PY - 2001/2/20
Y1 - 2001/2/20
N2 - Intratracheal (IT) injection of the transgene for human manganese super-oxide 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 over-expression of SOD2 in the SP1-SOD2 mice may have made the mice more sensitive to irradiation.
AB - Intratracheal (IT) injection of the transgene for human manganese super-oxide 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 over-expression of SOD2 in the SP1-SOD2 mice may have made the mice more sensitive to irradiation.
KW - MnSOD
KW - Radiation lung damage
KW - Radioprotective gene therapy
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U2 - 10.1002/1097-0215(20010220)96:1<11::AID-IJC2>3.0.CO;2-R
DO - 10.1002/1097-0215(20010220)96:1<11::AID-IJC2>3.0.CO;2-R
M3 - Article
C2 - 11241326
AN - SCOPUS:0035916343
SN - 0020-7136
VL - 96
SP - 11
EP - 21
JO - International journal of cancer
JF - International journal of cancer
IS - 1
ER -