The gene suicide system NTR/CB1954 causes ablation of differentiated 3T3L1 adipocytes by apoptosis
The gene suicide system NTR/CB1954 causes ablation of differentiated 3T3L1 adipocytes by apoptosis
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DOI：
10.4067/s0716-97602004000300009
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发表时间：
2004-01-01
影响因子：
6.7
通讯作者：
CLARK, JOHN A
中科院分区：
文献类型：
--
作者：
FELMER, RICARDO N;CLARK, JOHN A
描述了消融分化的脂肪细胞的可行性以及使用合适的前药活化系统消融细胞的机制。该系统基于E.一种大肠杆菌硝基还原酶（NTR），可将某些硝基化合物（如抗肿瘤药物CB 1954）活化为细胞毒性DNA链间交联剂。用aP2驱动的硝基还原酶构建体转染的分化的前脂肪细胞（3T3L1）在与含有前药CB 1954的培养基孵育后被有效杀死，而未转染的细胞不受影响。结果表明，细胞消融的机制是凋亡，并且该系统具有由前药的毒性代谢产物介导的旁观者效应。所描述的系统应该提供用于基因治疗研究的良好的替代方法和操纵转基因动物组织中的细胞数量的新的诱导方法以及研究组织从细胞损伤或损失中恢复的能力。
The feasibility of ablating differentiated adipocytes and the mechanism of cell ablation with a suitable prodrug activating system is described. The system is based on the use of E. coli nitroreductase (NTR) enzyme that activates certain nitro compounds, such as the antitumor drug CB1954, into cytotoxic DNA interstrand cross-linking agents. Differentiated preadipocyte cells (3T3L1) transfected with an aP2 driven nitroreductase construct were efficiently killed after incubation with medium containing the prodrug CB1954, while untransfected cells were not affected. It was demonstrated that the mechanism of cell ablation is apoptosis and that the system has a bystander effect mediated by a toxic metabolite of the prodrug. The described system should provide a good alternative approach for gene therapy studies and a new inducible approach to manipulating the number of cells in tissues of transgenic animals and the ability to study the recovery of the tissue from cell damage or loss.