Characteristics of cancer cell death after exposure to cytotoxic drugs in vitro.
Characteristics of cancer cell death after exposure to cytotoxic drugs in vitro.
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DOI：
10.1038/bjc.1996.10
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发表时间：
1996-01
影响因子：
8.8
通讯作者：
Tattersall, MHN
中科院分区：
文献类型：
--
作者：
Huschtscha, LI;Bartier, WA;Ross, CEA;Tattersall, MHN
研究了CCRF-CEM暴露后的细胞死亡特征。F2细胞对5种药物有较宽的浓度范围；这些是糖皮质激素地塞米松（DXM），有丝分裂抑制剂长春新碱（VIN）和三种抗代谢产物，甲氨蝶呤（MTX）， 5'-氟-2'-脱氧尿苷（FUdR）和5'-氟尿嘧啶（5- fu）。通过检测DNA降解模式、细胞形态和流式细胞术图谱，以及72小时内对细胞生长的影响，在不同时间监测药物处理细胞的细胞死亡机制。在生长抑制药物浓度下，第一个变化是药物暴露4-6小时后可检测到的细胞周期扰动。CCRF-CEM在所有药物治疗后均出现凋亡细胞死亡特征。F2细胞系，但模式和动力学变化很大。VIN在12 h诱导细胞凋亡变化，而DXM仅在48 h后才引起细胞凋亡。MTX和FUdR在核体间DNA切割前至少24 h诱导细胞凋亡的形态学变化，48 h后才检测到。相比之下，5-FU在任何浓度下均未引起核体间DNA切割，尽管在24 h前就存在形态学上的凋亡细胞。这些数据表明，药物治疗引起的细胞周期中断可能是启动濒死细胞药物特异性凋亡序列的常见触发因素。
The characteristics of cell death were investigated after exposure of CCRF-CEM.f2 cells to five drugs over a broad concentration range; these were the glucocorticoid dexamethasone (DXM), the mitotic inhibitor vincristine (VIN) and three antimetabolites, methotrexate (MTX), 5'-fluoro-2'-deoxyuridine (FUdR) and 5'-fluorouracil (5-FU). Drug-treated cells were monitored for cell death mechanisms at different times by examining the pattern of DNA degradation, cell morphology and flow cytometric profile, together with effects on cell growth over 72 h. At growth-inhibitory drug concentrations, the first changes were cell cycle perturbations detectable after 4-6 h of drug exposure. The appearance of features characteristic of apoptotic cell death was noted after all drug treatments in the CCRF-CEM.f2 cell line, but the pattern and kinetics varied considerably. VIN induced apoptotic changes by 12 h, while DXM treatment caused apoptosis only after 48 h. Both MTX and FUdR induced morphological changes characteristic of apoptosis at least 24 h before internucleosomal DNA cleavage, which was detectable only after 48 h. In contrast, 5-FU did not cause internucleosomal DNA cleavage by 48 h at any concentration, despite the presence of morphologically apoptotic cells 24 h earlier. These data suggest that disruption of the cell cycle caused by drug treatment may be the common trigger initiating the drug-specific apoptotic sequence of dying cells.
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DOI：
10.1111/j.1365-2184.1986.tb00683.x
发表时间：
1986-05-01
期刊：
CELL AND TISSUE KINETICS
影响因子：
--
作者：
DYSON, JED;SIMMONS, DM;BIRD, CC
通讯作者：
BIRD, CC
DOI：
10.1006/bbrc.1993.1794
发表时间：
1993-07-15
影响因子：
3.1
作者：
OLIVER, FJ;MARVEL, J;LOPEZRIVAS, A
通讯作者：
LOPEZRIVAS, A
影响因子：
64.5
作者：
LOWE, SW;RULEY, HE;HOUSMAN, DE
通讯作者：
HOUSMAN, DE
影响因子：
5.8
作者：
BARRY, MA;BEHNKE, CA;EASTMAN, A
通讯作者：
EASTMAN, A
影响因子：
6.1
作者：
RAFFRAY, M;COHEN, GM
通讯作者：
COHEN, GM