KINETIC AND PHYSICAL STUDIES OF CELL-DEATH INDUCED BY CHEMOTHERAPEUTIC-AGENTS OR HYPERTHERMIA
KINETIC AND PHYSICAL STUDIES OF CELL-DEATH INDUCED BY CHEMOTHERAPEUTIC-AGENTS OR HYPERTHERMIA
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DOI：
10.1111/j.1365-2184.1986.tb00683.x
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发表时间：
1986-05-01
期刊：
影响因子：
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通讯作者：
BIRD, CC
中科院分区：
文献类型：
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作者：
DYSON, JED;SIMMONS, DM;BIRD, CC
三个物理参数的动力学：细胞密度，相对细胞质粘度和DNA变性的稳定性已被测量在高温，甲基强的松龙和一系列癌症化疗药物诱导的细胞死亡之前的一段时间。这一系列的测量采用培养的人淋巴母细胞作为实验系统，以建立在细胞死亡的早期阶段可以观察到的变化，然后将这些测量应用于来自实体人类肿瘤的组织活检。细胞死亡，由高达43 ℃的高温诱导。C，甲基强的松龙，长春新碱，5-氟尿嘧啶，BCNU和美法仑，表现出基本相同的和可重复的变化，对应于那些表征程序性细胞死亡（凋亡）。这种变化也可以在43 ℃以上的高温后观察到。C，但重复性差，细胞膜损伤明显增加。在用阿霉素或甲氨蝶呤处理的细胞中，未检测到显示细胞密度增加的细胞亚群。DNA稳定性的测量很容易进行流式细胞荧光测定法，从而允许快速定量的细胞死亡的早期阶段的细胞的分数。改良的流式细胞仪将进一步允许测量细胞质粘度作为指示进入程序性细胞死亡的附加参数。这表明，这些测量可以很容易地应用于来自肿瘤组织活检的细胞悬液，以更准确地评估肿瘤生长速率，并允许在连续的肿瘤活检中监测对治疗的反应。
The kinetics of three physical parameters: cell density, relative cytoplasmic viscosity and DNA stability to denaturation have been measured during the period preceding cell death induced by hyperthermia, methylprednisolone and a series of cancer chemotherapeutic agents. This series of measurements employed cultured human lymphoblastoid cells as an experimental system to establish the changes that can be observed in the early stages of cell death, prior to applying such measurements to tissue biopsies from solid human tumours. Cell death, induced by hyperthermia up to 43.degree. C, methylprednisolone, vincristine, 5-fluorouracil, BCNU and melphalan, showed essentially identical and reproducible changes corresponding to those which characterize programmed cell death (apoptosis). Such changes could also be observed following hyperthermia above 43.degree. C, but reproducibility was poor and increasing damage to the cell membranes was evident. In cells treated with adriamycin or methotrexate, cell sub-populations showing an increase in cell density were not detected. Measurements of DNA stability were readily performed by flow cytofluorometry thus allowing rapid quantitation of the fraction of cells in the early stages of cell death. Modified flow cytometric instrumentation would further allow measurement of cytoplasmic viscosity as an additional parameter to indicate entry into programmed cell death. This suggests that these measurements could readily be applied to cell suspensions derived from tumour tissue biopsies for a more accurate assessment of tumour growth rate, and to allow monitoring of response to therapy in sequential tumour biopsies.