Enhancing effect of misonidazole on the response of the RIF-1 tumour to cyclophosphamide.
Enhancing effect of misonidazole on the response of the RIF-1 tumour to cyclophosphamide.
复制标题
米索硝唑对 RIF-1 肿瘤对环磷酰胺反应的增强作用。
DOI：
10.1038/bjc.1981.172
复制
发表时间：
1981
影响因子：
8.8
通讯作者：
Brown,JM
中科院分区：
文献类型：
--
作者：
Law,MP;Hirst,DG;Brown,JM
本文研究了米索咪唑（MISO）对环磷酰胺（CY）细胞毒性的影响。通过克隆试验中的生长延迟和细胞存活来测量RIF-1肿瘤的反应。MISO可增强CY的细胞毒性。单次注射MISO时，CY前30 min ~ 2 h注射MISO增强效果最好。增强比（即CY单药剂量除以CY与MISO联合使用引起相同反应所需的剂量）随MISO剂量的增加而增加，直至250 mg/kg，但随CY剂量的增加而降低，超过50 mg/kg。对于5次每日给药，CY剂量增加至约25 mg/kg/注射时增强作用增加。使用脾集落测定法测量骨髓干细胞的存活。MISO在100 mg/kg以下剂量对CY的细胞毒性无明显增强作用。在较高剂量下观察到增强，但效果低于肿瘤。CY减少了循环白色血细胞的数量。中性粒细胞耗竭最为严重。当CY与MISO联合给药时，WBC计数略低于CY单独给药后的WBC计数，但这种效应可以通过直接的MISO细胞毒性来解释。这些经验表明，如果MISO与临床范围内的CY剂量组合，则可以实现治疗增益。从实验进行调查可能涉及的机制，我们的结论是，对于RIF-1肿瘤的主要影响MISO是抑制从CY诱导的潜在致命损伤的修复。
The effect of misonidazole (MISO) on the cytotoxicity of cyclophosphamide (CY) was investigated in the mouse. The response of the RIF-1 tumour was measured by growth delay and by cell survival in a cloning assay. MISO enhanced the cytotoxicity of CY. For single treatment, enhancement was maximal when MISO was given 30 min to 2 h before CY. The enhancement ratio (ie the dose of CY alone divided by the dose of CY with MISO required to cause the same response) increased with increasing dose of MISO up to 250 mg/kg, but decreased with increasing dose of CY above 50 mg/kg. For 5 daily treatments, enhancement increased with CY dose up to approximately 25 mg/kg/injection. Survival of marrow stem cells was measured using the spleen-colony assay. MISO did not enhance significantly the cytotoxicity of CY at doses under 100 mg/kg. Enhancement was seen at higher doses, but the effect was less than in tumours. CY reduced the number of circulating white blood cells. Neutrophils were most severely depleted. The WBC count was slightly lower when CY was given in combination with MISO than after CY alone, but the effect could be accounted for by direct MISO cytotoxicity. These experiences suggest that a therapeutic gain may be achieved if MISO is combined with doses of CY in the clinical range. From experiments performed to investigated the possible mechanisms involved, we conclude that for the RIF-1 tumour the major effect of MISO is to inhibit the repair from CY-induced potentially lethal damage.