Lafleur M V, Loman H
Radiat Environ Biophys. 1986;25(3):159-73. doi: 10.1007/BF01221222.
Dilute aqueous solutions of biologically active DNA can serve as a simplified model system of the cell. As a biological endpoint the survival of the DNA (after transfection to E. coli spheroplasts) is used. Damage in the DNA, irradiated in water with gamma rays, can be ascribed to reactions with primary waterradicals. By introducing additives in such solutions, which will scavenge the primary waterradicals, competition between a scavenger and DNA for such radicals can be studied. Comparison of different additives makes it possible to decide whether a compound behaves like a simple scavenger, radiosensitizer or like a radioprotector. In this context work has been done with the electron-affinic radiosensitizers metronidazole, misonidazole and nifuroxime. We have found that these wellknown cellular sensitizers do not enhance the inactivation of biologically active DNA. They act as simple competitive scavenger for waterradicals. However, if besides a sensitizer a trace of a metalloporphyrin containing compound (e.g. cyt. c) is present during irradiation an enhanced DNA inactivation, which can be interpreted as sensitization, is observed. Without sensitizer metalloporphyrins induce an enhanced protection of DNA. Apart from these effects the consequences of both chemical-(sulphydryl) and enzymatic-(excision; recombination) repair has been studied. It has been found that sulphydryl compounds are able to react with DNA radicals, modifying the radiation damage in such a way that e.g. breaks are prevented. Further in double-stranded DNA a considerable amount of OH and also H radical damage appeared to be reparable by the excision-repair mechanism. However, post-replication repair had only very small or no effect on the amount of damage.
具有生物活性的DNA的稀水溶液可作为细胞的简化模型系统。作为生物学终点，使用DNA（转染至大肠杆菌原生质球后）的存活率。在水中用γ射线辐照的DNA损伤可归因于与初级水自由基的反应。通过在这种溶液中引入添加剂，这些添加剂将清除初级水自由基，可以研究清除剂与DNA之间对这些自由基的竞争。比较不同的添加剂可以确定一种化合物是表现为简单的清除剂、放射增敏剂还是放射防护剂。在这方面，已经对电子亲和性放射增敏剂甲硝唑、米索硝唑和硝呋肟进行了研究。我们发现，这些著名的细胞增敏剂不会增强具有生物活性的DNA的失活。它们作为水自由基的简单竞争性清除剂起作用。然而，如果在辐照期间除了增敏剂之外还存在痕量的含金属卟啉化合物（例如细胞色素c），则会观察到DNA失活增强，这可以解释为增敏作用。没有增敏剂时，金属卟啉会增强对DNA的保护。除了这些影响之外，还研究了化学（巯基）和酶促（切除；重组）修复的后果。已经发现巯基化合物能够与DNA自由基反应，以防止断裂等方式改变辐射损伤。此外，在双链DNA中，相当数量的OH和H自由基损伤似乎可通过切除修复机制修复。然而，复制后修复对损伤量的影响非常小或没有影响。
