Russo A, DeGraff W, Kinsella T J, Gamson J, Glatstein E, Mitchell J B
Int J Radiat Oncol Biol Phys. 1986 Aug;12(8):1371-4. doi: 10.1016/0360-3016(86)90174-4.
This study reports on the potentiation of selected chemotherapy drugs following halogenated pyrimidine incorporation into cellular DNA. Exponentially growing cultures of Chinese hamster V79 cells were exposed to 10(-5) M IdUrd or BrdUrd for 17 hr (approximately 2 cell doublings). This exposure resulted in approximately 16% replacement of thymidine by IdUrd or BrdUrd in the cellular DNA. Following the IdUrd exposure, dose response curves were determined for a 1 hr exposure to the various drugs. IdUrd pre-treatment was shown to enhance the cytotoxicity of melphalan, adriamycin, cisplatin, and neocarzinostatin with enhancement ratios at 1% survival of 1.5, 1.8, 1.5, and 1.4 respectively. BrdUrd pre-treatment also enhanced cisplatin cytotoxicity. A combination of BrdUrd pretreatment, cisplatin, and X rays was shown to yield additive survival effects. These findings are discussed in the context of possible clinical application of local drug perfusion of tumor-containing organs.
本研究报告了卤代嘧啶掺入细胞DNA后对某些化疗药物的增效作用。将指数生长的中国仓鼠V79细胞培养物暴露于10(-5)M碘脱氧尿苷（IdUrd）或溴脱氧尿苷（BrdUrd）中17小时（约2个细胞倍增时间）。这种暴露导致细胞DNA中约16%的胸腺嘧啶被IdUrd或BrdUrd取代。在IdUrd暴露后，测定了各种药物1小时暴露的剂量反应曲线。结果显示，IdUrd预处理可增强美法仑、阿霉素、顺铂和新制癌菌素的细胞毒性，在1%存活率时的增强率分别为1.5、1.8、1.5和1.4。BrdUrd预处理也增强了顺铂的细胞毒性。BrdUrd预处理、顺铂和X射线的联合应用显示出相加的存活效应。在含肿瘤器官局部药物灌注可能的临床应用背景下讨论了这些发现。
