BCL-2 ONCOGENE PROTECTS A BONE-MARROW-DERIVED PRE-B-CELL LINE FROM 5'-FLUOR,2' DEOXYURIDINE-INDUCED APOPTOSIS
BCL-2 ONCOGENE PROTECTS A BONE-MARROW-DERIVED PRE-B-CELL LINE FROM 5'-FLUOR,2' DEOXYURIDINE-INDUCED APOPTOSIS
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DOI：
10.1006/bbrc.1993.1794
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发表时间：
1993-07-15
影响因子：
3.1
通讯作者：
LOPEZRIVAS, A
中科院分区：
文献类型：
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作者：
OLIVER, FJ;MARVEL, J;LOPEZRIVAS, A
BCL-2原癌基因已被证明可以保护造血祖细胞免受白介素3(IL3)去除后细胞程序性死亡的影响。在本报告中，我们有证据表明，BCL-2在前B细胞系BAF3中的过表达可以保护细胞免受胸腺扩张合成酶抑制剂5‘-氟，2’-脱氧尿苷(FDUR)在IL-3存在下诱导的细胞凋亡。剂量-反应实验分析细胞死亡与药物浓度的关系表明，BAF3bCL-2对FDUR具有明显的耐药性。在BAF3细胞中观察到DNA被切割成寡核小体长度的片段，这是细胞凋亡的一个特征，而在高表达bcl2的细胞中DNA切割受到抑制。我们已经确定了FDUR治疗后dATP和dTTP池的变化。有趣的是，在dNTP池变化的动力学方面，两个细胞之间没有发现差异。因此，Bcl2蛋白对dNTP失衡诱导的细胞凋亡的保护作用必须归因于DNA前体合成的扰动下游和染色质的核内裂解激活之前的一步。
Thebcl-2protooncogene has been shown to protect haemopoietic precursors from programmed cell death after the removal of interleukin-3 (IL3). In the present report we show evidence that overexpression ofbcl-2in the pre-B-cell line BAF3 protects cells from apoptosis induced by treatment with the thymydilate synthase inhibitor 5′-fluor,2′-deoxyuridine (FDUR) in the presence of IL-3. Dose-response experiments analyzing the dependence of cell death on drug concentration indicated a marked resistence of BAF3bcl-2to FDUR treatment. Cleavage of DNA into oligonucleosome-length fragments, a characteristic of apoptosis, was observed in BAF3 cells and inhibited in the cells overexpressingbcl-2. We have determined variations in the dATP and dTTP pools after FDUR treatment. Interestingly, no differences were found between both cells in the kinetics of changes in dNTP pools. Therefore, the protective effect of theBcl-2protein on apoptosis induced by dNTP unbalance must be ascribed to a step downstream of perturbations in the synthesis of DNA precursors and before activation of endonucleolytic cleavage of chromatin.