抗人类免疫缺陷病毒药物3'-氟胸苷可诱导人淋巴母细胞发生DNA损伤和凋亡。
The anti-human immunodeficiency virus agent 3'-fluorothymidine induces DNA damage and apoptosis in human lymphoblastoid cells.
作者信息
Sundseth R, Joyner S S, Moore J T, Dornsife R E, Dev I K
机构信息
Division of Biochemistry, Wellcome Research Laboratories, Research Triangle Park, North Carolina 27709, USA.
出版信息
Antimicrob Agents Chemother. 1996 Feb;40(2):331-5. doi: 10.1128/AAC.40.2.331.
Abstract
Patients infected with the human immunodeficiency virus experienced severe hematopoietic toxicity after treatment with the deoxynucleoside analog 3'-fluorothymidine (FLT). Using several methods for the analysis of genome integrity, including histochemical staining of the 3' ends of DNA and both conventional and pulsed-field agarose gel electrophoresis, we demonstrated that FLT caused extensive DNA fragmentation in CEM cells that was not observed when these cells were treated with other, less toxic thymidine analogs. In addition, a distinctive pattern of small DNA fragments that is characteristic of cells in the process of programmed cell death was observed in the genomic DNA of CEM cells treated with FLT. We conclude that FLT induces DNA fragmentation and apoptosis in a human cell line of hematopoietic origin, and we offer this observation as a possible explanation for the severe toxicity of FLT observed in vivo.
摘要
感染人类免疫缺陷病毒的患者在接受脱氧核苷类似物3'-氟胸苷（FLT）治疗后出现严重的造血毒性。我们使用了多种分析基因组完整性的方法，包括DNA 3'末端的组织化学染色以及常规和脉冲场琼脂糖凝胶电泳，结果表明FLT在CEM细胞中导致广泛的DNA片段化，而当这些细胞用其他毒性较小的胸苷类似物处理时未观察到这种情况。此外，在用FLT处理的CEM细胞的基因组DNA中观察到一种独特的小DNA片段模式，这是程序性细胞死亡过程中细胞的特征。我们得出结论，FLT在造血来源的人类细胞系中诱导DNA片段化和凋亡，我们将这一观察结果作为体内观察到的FLT严重毒性的一种可能解释。
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