Hirst D G, Brown J M, Hazlehurst J L
Br J Cancer. 1982 Jul;46(1):109-16. doi: 10.1038/bjc.1982.172.
Enhancement of CCNU cytotoxicity by misonidazole (MISO) was studied in three tumours and two normal tissues in the mouse. The 3 experimental tumours (SCCVII/St, EMT6 and KHT) showed very different sensitivities to CCNU alone, but MISO enhanced the cell killing in ech case. The effect was not always dose-modifying, so that the CCNU dose range for the greatest enhancement was different in each of the tumours. In all 3 tumours, enhancement increased with dose of MISO. The effect on two normal tissues, marrow (CFU-S) and testis (spermatogonia), was also investigated. Enhancement of marrow toxicity could be demonstrated only at CCNU doses greater than 12.5 mg/kg, so that at lower CCNU doses there was a therapeutic gain equal to the tumour enhancement ratio. The spermatogonia effect, however, showed enhancement by MISO similar to that seen in the tumours at all CCNU doses up to 20 mg/kg.
在小鼠的三种肿瘤和两种正常组织中研究了米索硝唑（MISO）对洛莫司汀（CCNU）细胞毒性的增强作用。三种实验性肿瘤（SCCVII/St、EMT6和KHT）对单独使用的CCNU表现出非常不同的敏感性，但MISO在每种情况下均增强了细胞杀伤作用。这种作用并不总是具有剂量修饰性，因此每种肿瘤中实现最大增强效果的CCNU剂量范围各不相同。在所有三种肿瘤中，增强作用均随MISO剂量的增加而增强。还研究了其对两种正常组织，即骨髓（CFU-S）和睾丸（精原细胞）的作用。仅在CCNU剂量大于12.5 mg/kg时才能证明骨髓毒性增强，因此在较低的CCNU剂量下，治疗获益等同于肿瘤增强率。然而，在高达20 mg/kg的所有CCNU剂量下，精原细胞效应显示MISO的增强作用与肿瘤中所见相似。
