Lehnert S
Cancer Chemother Pharmacol. 1986;16(3):269-72. doi: 10.1007/BF00293990.
The toxicities of three phenothiazines, promazine, chlorpromazine, and trifluoperazine, towards cells of a mouse fibrosarcoma were quantified by means of an in vitro assay of clonogenic cell survival. For all three drugs cell kill was proportional to the amount of drug injected. Following injection of equimolar (0.2 mM/kg) amounts, cell survival was progressively reduced for a period of at least 48 h. On the basis of cell survival at 48 h after administration the ranking of the drugs for cytotoxicity, in ascending order, was trifluoperazine, chlorpromazine, promazine. A period of acute hypoxia prior to processing of the tumor did not enhance the toxicity of any of the drugs, and no change in the size of the hypoxic fraction of the tumor was seen 24 h after the injection of chlorpromazine. On this basis it was concluded that there was no evidence of enhanced toxicity of drugs for either chronically or acutely hypoxic tumor cells. A reduction in the number of clonogenic tumor cells per gram of tumor was largely the result of a fall in the number of viable cells recovered from the tumor. The plating efficiency of surviving cells remained constant or was only slightly depressed.
通过克隆形成细胞存活的体外测定法，对三种吩噻嗪类药物，即丙嗪、氯丙嗪和三氟拉嗪，对小鼠纤维肉瘤细胞的毒性进行了定量分析。对于所有这三种药物，细胞杀伤与注射的药物量成正比。注射等摩尔量（0.2 mM/kg）后，细胞存活率在至少48小时内逐渐降低。根据给药后48小时的细胞存活率，三种药物的细胞毒性排名由低到高依次为三氟拉嗪、氯丙嗪、丙嗪。在处理肿瘤之前的急性缺氧期并未增强任何一种药物的毒性，注射氯丙嗪24小时后，肿瘤缺氧部分的大小未见变化。据此得出结论，没有证据表明药物对慢性或急性缺氧肿瘤细胞的毒性增强。每克肿瘤中克隆形成肿瘤细胞数量的减少主要是由于从肿瘤中回收的活细胞数量下降所致。存活细胞的接种效率保持不变或仅略有降低。
