Cotter T G, Glynn J M, Echeverri F, Green D R
Division of Cellular Immunology, La Jolla Institute for Allergy and Immunology, CA 92037.
Anticancer Res. 1992 May-Jun;12(3):773-9.
A1.1 T-cell hybridoma cells exposed to either actinomycin D (1 microgram/ml), camptothecin (200 ng/ml) or aphidicolin (10 micrograms/ml) for 16 hrs at 37 degrees C die via apoptosis. The cell death was independent of RNA synthesis, in contrast to previous data reported for other forms of apoptosis in murine lymphocyte cells and their derived lines. Each of the three agents described appeared to induce death in all phases of the cell cycle in asynchronously proliferating cells. G1 cells appeared to be more susceptible to the effects of camptothecin and contrasts with other reports which detail its selectivity for S and G2 phase cells. This might indicate that cells are progressing into S phase before dying or, alternatively, cells may indeed be dying in G1. When elutriated synchronised cells were exposed to each of the three cytotoxic agents cell death occurred in all phases of the cell cycle. In view of the fact that G1 and S phase cells did not cycle to any appreciable extent during drug exposure, it was likely that ensuing death, occurred specifically from these phases. G2/M cells, however, moved rapidly into G1 in the presence of each drug, thus making it difficult to determine whether G2/M cells were capable of undergoing drug-induced apoptosis. To overcome this problem, nocodazole (50 ng/ml) was used to block asynchronous cells in M phase. When these cells were exposed to actinomycin D, aphidicolin or camptothecin, cell death ensued via apoptosis.
A1.1 将T细胞杂交瘤细胞在37℃下分别暴露于放线菌素D(1微克/毫升)、喜树碱(200纳克/毫升)或阿非迪霉素(10微克/毫升)16小时,细胞会通过凋亡死亡。与先前报道的小鼠淋巴细胞及其衍生系中其他形式的凋亡数据相反,这种细胞死亡与RNA合成无关。上述三种药物中的每一种似乎都能在异步增殖细胞的细胞周期的所有阶段诱导细胞死亡。G1期细胞似乎对喜树碱的作用更敏感,这与其他详细描述其对S期和G2期细胞具有选择性的报道形成对比。这可能表明细胞在死亡前正在进入S期,或者,细胞可能确实在G1期死亡。当用淘析法同步化的细胞暴露于这三种细胞毒性药物中的每一种时,细胞死亡发生在细胞周期的所有阶段。鉴于在药物暴露期间G1期和S期细胞没有明显的循环,随后的死亡很可能是由这些阶段特异性发生的。然而,G2/M期细胞在每种药物存在的情况下迅速进入G1期,因此很难确定G2/M期细胞是否能够经历药物诱导的凋亡。为了克服这个问题,使用诺考达唑(50纳克/毫升)将异步细胞阻滞在M期。当这些细胞暴露于放线菌素D、阿非迪霉素或喜树碱时,细胞会通过凋亡死亡。