STANDARDIZED KINETIC MICROASSAY TO QUANTIFY DIFFERENTIAL CHEMOSENSITIVITY ON THE BASIS OF PROLIFERATIVE ACTIVITY
STANDARDIZED KINETIC MICROASSAY TO QUANTIFY DIFFERENTIAL CHEMOSENSITIVITY ON THE BASIS OF PROLIFERATIVE ACTIVITY
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DOI：
10.1007/bf01192309
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发表时间：
1992-01-01
影响因子：
3.6
通讯作者：
SCHOENENBERGER, H
中科院分区：
文献类型：
--
作者：
BERNHARDT, G;REILE, H;SCHOENENBERGER, H
常规地，体外细胞毒性测定作为单终点测定进行。为了补偿不同细胞系之间的生长速率的多样性，在本报告中，我们描述了一种计算机化的动力学化学敏感性测定的基础上定量的生物量与结晶紫染色细胞。作为先决条件，四种人乳腺癌细胞系（MDA-MB-231、MCF-7、T-47-D和ZR-75-1）根据培养物中的传代次数表征雌激素和孕激素受体含量、模态染色体数目和增殖动力学。随着ZR-75-1暴露于不同浓度顺铂的培养时间延长，观察到药物效应呈剂量相关性增加。由于对初始细胞质量的T/C值进行了校正（在加入药物时），在校正的T/C值与孵育时间的曲线图中，细胞抑制和细胞杀灭药物作用之间的明显区别变得明显。未处理的控制校正的T/C值和可能的时间过程中的理论抑制曲线（反映细胞生长抑制，短暂的细胞毒性或杀细胞药物的作用，以及耐药性的发展）和它们的关系，相应的药物处理的细胞的生长曲线的影响进行了讨论。用己烯雌酚二丙酸酯、他莫昔芬、美法仑、顺铂、长春碱、阿霉素和5-氟尿嘧啶进行的化学敏感性测定证明了理论考虑在实践中对MDA-MB-231、MCF-7、T-47-D和ZR-75-1人乳腺癌细胞系是正确的。
Conventionally in vitro cytotoxicity assays are performed as single-end-point determinations. To compensate for the diversity of growth rates among different cell lines in this report we describe a computerized kinetic chemosensitivity assay based on quantification of biomass by staining cells with crystal violet. As a prerequisite four human breast cancer cell lines (MDA-MB-231, MCF-7, T-47-D and ZR-75-1) were characterized with regard to oestrogen and progesterone receptor content, modal chromosome number and proliferation kinetics depending on the number of passages in culture. With prolonged time in culture for ZR-75-1 exposed to various concentrations of cisplatinum a dose-related increase in drug effect was observed. Owing to a correction of the T/C values for the initial cell mass (at the time when drug is added) a sharp distinction between cytostatic and cytocidal drug effects becomes obvious in plots of corrected T/C values versus time of incubation. The influence of the untreated control on the corrected T/C values and possible time courses of theoretical inhibition profiles (reflecting cytostatic, transient cytotoxic or cytocidal drug effects as well as development of resistance) and their relationship to the corresponding growth curves of drug-treated cells are discussed. Chemosensitivity assays with diethylstilbestrol dipropionate, tamoxifen, melphalan, cisplatinum, vinblastine, Adriamycin and 5-fluorouracil prove the theoretical considerations to be true for MDA-MB-231, MCF-7, T-47-D and ZR-75-1 human breast cancer cell lines in practice.