Greenberger Joel S, Epperly Michael W
Department of Radiation Oncology, University of Pittsburgh Cancer Institute, 200 Lothrop Street, Pittsburgh, PA 15213, USA.
In Vivo. 2007 Mar-Apr;21(2):141-6.
Administration of manganese superoxide dismutase-plasmid liposomes (MnSOD-PL) has been demonstrated to provide local radiation protection to the lung, esophagus, oral cavity, urinary bladder and intestine. Radiation protection has been shown to be mediated in part by MnSOD stabilization of the antioxidant pool including glutathione and total thiols within cells and in normal tissues. In experiments to determine whether organ-specific radioprotection would also protect orthotopic tumors, mice with Lewis lung carcinoma orthotopically placed at the carina or in other experiments with mice with cheek pouch placed SCCVII orthotopic squamous cell tumors demonstrated paradoxical and beneficial tumor radiosensitization following intratracheal or intraoral MnSOD-PL, respectively. The mechanism of MnSOD-PL tumor radiosensitization may involve a difference in redox balance between tumors and normal tissues. Differences in handling radiation-induced oxidative stress between tumors and normal tissues can provide a fundamental basis to design new cancer therapeutic agents which can exploit differences between normal tissue and tumor mechanisms of handling the oxidative stress of ionizing irradiation damage.
已证明给予锰超氧化物歧化酶-质粒脂质体（MnSOD-PL）可为肺、食管、口腔、膀胱和肠道提供局部辐射防护。辐射防护作用已被证明部分是由MnSOD稳定抗氧化物质库介导的，该抗氧化物质库包括细胞内和正常组织中的谷胱甘肽和总硫醇。在确定器官特异性辐射防护是否也能保护原位肿瘤的实验中，将Lewis肺癌原位接种于隆突处的小鼠，或在其他实验中，将SCCVII原位鳞状细胞肿瘤接种于颊囊的小鼠，分别经气管内或口腔内给予MnSOD-PL后，均表现出矛盾但有益的肿瘤放射增敏作用。MnSOD-PL肿瘤放射增敏的机制可能涉及肿瘤与正常组织之间氧化还原平衡的差异。肿瘤与正常组织在处理辐射诱导的氧化应激方面的差异可为设计新的癌症治疗药物提供基本依据，这些药物可利用正常组织与肿瘤处理电离辐射损伤氧化应激机制之间的差异。
