Hahn S M, Krishna C M, Samuni A, DeGraff W, Cuscela D O, Johnstone P, Mitchell J B
Radiation Biology Section, National Cancer Institute, NIH, Bethesda, Maryland 20892.
Cancer Res. 1994 Apr 1;54(7 Suppl):2006s-2010s.
The identification of radioprotectors is an important goal for those involved in radiation oncology and for those interested in the investigation of the mechanisms of radiation cytotoxicity. Recently, a new class of in vitro and in vivo radioprotectors, the nitroxides, has been discovered. The nitroxides are low-molecular-weight stable free radicals which are freely membrane permeable and which have been shown to act as superoxide dismutase mimics. Further investigation of these compounds has shown that a water-soluble nitroxide, Tempol, protects cultured Chinese hamster V79 cells from the cytotoxicity caused by superoxide, hydrogen peroxide, and t-butyl hydroperoxide. Tempol and five other water-soluble nitroxides have also been shown to protect V79 cells against radiation-induced cytotoxicity. Potential mechanisms of protection by the nitroxides include oxidation of reduced transition metals, superoxide dismutase-like activity, and scavenging of oxy- and carbon-based free radicals. In vivo studies reveal that Tempol protects C3H mice from the lethal effects of radiation with a dose causing 50% lethality within 30 days of 9.97 Gy and 7.84 Gy in Tempol-treated and saline-treated mice, respectively, and a dose modification factor of 1.3. The nitroxides represent a new class of non-thiol radioprotectors which may also have application as general antioxidants. Additional work is necessary to screen other nitroxides for in vivo radioprotection and toxicity as well as to fully evaluate the extent to which these compounds protect tumors.
对于从事放射肿瘤学的人员以及对辐射细胞毒性机制研究感兴趣的人员来说，鉴定辐射防护剂是一个重要目标。最近，已发现一类新型的体外和体内辐射防护剂——氮氧化物。氮氧化物是低分子量的稳定自由基，可自由透过细胞膜，并且已证明其具有超氧化物歧化酶模拟物的作用。对这些化合物的进一步研究表明，一种水溶性氮氧化物Tempol可保护培养的中国仓鼠V79细胞免受超氧化物、过氧化氢和叔丁基过氧化氢所引起的细胞毒性。Tempol和其他五种水溶性氮氧化物也已证明可保护V79细胞免受辐射诱导的细胞毒性。氮氧化物的潜在保护机制包括还原过渡金属的氧化、超氧化物歧化酶样活性以及清除氧自由基和碳自由基。体内研究表明，Tempol可保护C3H小鼠免受辐射的致死效应，在Tempol处理组和生理盐水处理组小鼠中，分别在30天内导致50%致死率的剂量为9.97 Gy和7.84 Gy，剂量修正因子为1.3。氮氧化物代表一类新型的非硫醇辐射防护剂，其也可能用作一般抗氧化剂。还需要开展更多工作来筛选其他氮氧化物的体内辐射防护作用和毒性，以及全面评估这些化合物对肿瘤的保护程度。
