Hill B T, Whelan R D
J Natl Cancer Inst. 1981 Aug;67(2):437-43.
Survival curves for several monolayer and suspension cultures following 24-hour exposures to various vincristine (VCR) or vindesine (VDS) concentration were all of the exponential-plateau type. Cytotoxicity increased with duration of exposure in hamster NIL8 cells and was comparable for both drugs. Murine L5178Y cells, although 200 times more sensitive than NIL8 cells, also showed similar sensitivities to VCR and VDS. Murine neuroblastoma cells proved approximately fivefold less sensitive to VDS than VCR, whereas qualitative and quantitative differences in the activity of these two drugs were noted in human neuroblastoma cells. The lethal effects of VCR and VDS were exerted solely on logarithmically growing NIL8 cells in the S-phase. Plateau-phase human neuroblastoma cells were also significantly less sensitive to both drugs than were logarithmically growing populations, were cell kill occurred during the S-phase. Complete mitotic arrest, induced by a 24-hour exposure to VCR or VDS, was only partially reversible, whereas rapid and complete reversibility occurred after only 5 hours of drug exposure.
几种单层培养和悬浮培养的细胞在暴露于不同长春新碱(VCR)或长春地辛(VDS)浓度24小时后的存活曲线均为指数-平台型。仓鼠NIL8细胞的细胞毒性随暴露时间延长而增加,两种药物的细胞毒性相当。小鼠L5178Y细胞虽然比NIL8细胞敏感200倍,但对VCR和VDS也表现出相似的敏感性。小鼠神经母细胞瘤细胞对VDS的敏感性比VCR低约五倍,而在人神经母细胞瘤细胞中观察到这两种药物活性的定性和定量差异。VCR和VDS的致死作用仅作用于处于S期对数生长期的NIL8细胞。平台期的人神经母细胞瘤细胞对这两种药物的敏感性也明显低于对数生长期的细胞群体,细胞杀伤发生在S期。暴露于VCR或VDS 24小时诱导的完全有丝分裂停滞仅部分可逆,而仅在药物暴露5小时后就出现快速且完全的可逆性。