Epperly M W, Travis E L, Whitsett J A, Raineri I, Epstein C J, Greenberger J S
Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA.
Int J Cancer. 2001 Feb 20;96(1):11-21. doi: 10.1002/1097-0215(20010220)96:1<11::aid-ijc2>3.0.co;2-r.
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.
在照射前经气管内（IT）注射质粒/脂质体（SOD2-PL）复合物中的人锰超氧化物歧化酶转基因，可保护C57BL/6J小鼠免受全肺照射诱导的机化性肺泡炎/纤维化。在基因治疗后48小时，在培养的肺泡II型（AT-II）细胞和气管支气管树细胞中检测到转基因mRNA。为了确定在全肺或表面活性剂启动子限制的AT-II细胞（SP1）-SOD2小鼠中组成型过表达小鼠MnSOD（Sod2）是否会提供内在的抗辐射性，将两株转基因小鼠与年龄匹配的对照进行了比较。其他组的表面活性剂启动子限制（SP1）-SOD2转基因小鼠或对照FeVB/NHsd小鼠在照射前接受了IT SOD2-PL基因治疗。两种MnSOD转基因小鼠品系均未显示出显著的内在肺保护作用。SP1-SOD2转基因小鼠在照射前24小时经IT注射人SOD2-PL复合物可免受肺损伤。因此，转基因小鼠肺中人SOD2或小鼠Sod2的过表达均不能提供内在的肺照射保护。SP1-SOD2小鼠中SOD2的过表达可能使小鼠对辐射更敏感。
