Zwacka R M, Dudus L, Epperly M W, Greenberger J S, Engelhardt J F
Department of Anatomy and Cell Biology, University of Iowa, Iowa City 52242-1109, USA.
Hum Gene Ther. 1998 Jun 10;9(9):1381-6. doi: 10.1089/hum.1998.9.9-1381.
Toxicity to nontumor-derived tissue has proven to be a significant obstacle in achieving therapeutic levels of gamma irradiation in the treatment of cancer. The formation of reactive oxygen species (ROS) such as superoxide radicals (O2-) following irradiation is thought to be a major determinant of cellular damage. To this end, we describe the generation of two recombinant adenoviral vectors expressing the radical-scavenging enzymes MnSOD and CuZnSOD to test therapeutic strategies of radioprotection. Using a human lung epithelial cell line (IB-3), we have demonstrated that infections with both Ad.CMVMnSOD or Ad.CMVCuZnSOD significantly increase both the levels of SOD protein and enzymatic activity as compared to control cells. This increase in SOD expression reduced the level of apoptosis at 72 hr post-irradiation by 50% as compared to mock- or Ad.CMVLacZ-infected cells. Such studies provide the foundation for radioprotective gene therapies in the treatment of cancer.
事实证明，对非肿瘤来源组织的毒性是在癌症治疗中实现伽马射线治疗剂量的一个重大障碍。辐射后诸如超氧阴离子自由基（O2-）等活性氧物质（ROS）的形成被认为是细胞损伤的主要决定因素。为此，我们描述了两种表达自由基清除酶MnSOD和CuZnSOD的重组腺病毒载体的产生，以测试辐射防护的治疗策略。使用人肺上皮细胞系（IB-3），我们已经证明，与对照细胞相比，用Ad.CMVMnSOD或Ad.CMVCuZnSOD感染均显著增加了SOD蛋白水平和酶活性。与模拟感染或Ad.CMVLacZ感染的细胞相比，SOD表达的这种增加使辐射后72小时的细胞凋亡水平降低了50%。此类研究为癌症治疗中的辐射防护基因疗法奠定了基础。
