Osieka R, Glatte P, Haedecke U, Schmidt C G
Strahlentherapie. 1982 Oct;158(10):620-9.
In addition to the well-known radiosensitizing properties of misonidazole its potential for chemosensitization has been investigated recently. According to results obtained mostly with conventional murine tumor systems, the degree of such chemosensitization depends on the particular tumor system, the type of antineoplastic agent and the dose of misonidazole employed. Our experiments were conducted with a human melanoma transplanted onto (nu/nu) mice. At the dose level of 1 g/kg misonidazole toxicity was enhanced by a factor of about 3, whereas antineoplastic activity was enhanced only by a factor of about 1.8. Therefore, the usefulness of such chemosensitization remains limited, especially since under clinical circumstances this dose of misonidazole would cause unacceptable neurotoxicity. The retention of radiotivity from 14C-MeCCNU is increased in neoplastic as well as in normal tissues by a factor of 1.3.DNA interstrand crosslinks measured 24 hours after drug exposure, however, are increased by a factor of about 2. Despite their nonselective reaction at the level of molecular pharmacology, drugs with sensitizing or protective properties may well constitute a valuable addition to the serial synthesis of chemical congeners in drug development. The use of oxazaphosphorines is quoted as an example where selective protection from urotoxicity is afforded by sodium-2-mercaptoethanesulfonate.
除了已知的米索硝唑的放射增敏特性外，其化学增敏潜力最近也得到了研究。根据大多在传统小鼠肿瘤系统中获得的结果，这种化学增敏的程度取决于特定的肿瘤系统、抗肿瘤药物的类型以及所使用的米索硝唑剂量。我们的实验是用移植到（裸/裸）小鼠身上的人黑色素瘤进行的。在米索硝唑剂量为1 g/kg时，毒性增强了约3倍，而抗肿瘤活性仅增强了约1.8倍。因此，这种化学增敏的实用性仍然有限，特别是因为在临床情况下，这个剂量的米索硝唑会导致不可接受的神经毒性。14C-甲环亚硝脲在肿瘤组织和正常组织中的放射性保留增加了1.3倍。然而，在药物暴露24小时后测量的DNA链间交联增加了约2倍。尽管它们在分子药理学水平上的反应是非选择性的，但具有增敏或保护特性的药物很可能成为药物开发中化学同系物系列合成的有价值补充。以氧氮磷杂环化合物的使用为例，2-巯基乙烷磺酸钠可对尿路毒性提供选择性保护。
