首页> 外文期刊>Cell biology international. >DOES THE BCR/ABL-MEDIATED INCREASE IN THE EFFICACY OF DNA REPAIR PLAY A ROLE IN THE DRUG RESISTANCE OF CANCER CELLS?
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DOES THE BCR/ABL-MEDIATED INCREASE IN THE EFFICACY OF DNA REPAIR PLAY A ROLE IN THE DRUG RESISTANCE OF CANCER CELLS?

机译:BCR / ABL介导的DNA修复效率是否在癌细胞的耐药性中发挥作用?

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BCR/ABL oncogenic tyrosine kinase is responsible for the pathogenesis of Philadelphia chromosome-positive human leukemia and is generated by a specific reciprocal chromosome translocation, t(9;22)(q34-;q11+). We examined the role of DNA repair in therapeutic drug resistance to idarubicin in the murine pro-B lymphoid cell line BaF3 and its BCR/ABL -transformed clone. These cells can be used as models of human leukemias. The MTT assay revealed that BCR/ABL -transformed cells displayed resistance to idarubicin in the range 0.3-0.5 &mgr;m, compared with the control BaF3 cells. Idarubicin at 0.3 and 1 &mgr;m induced DNA damage in the form of strand-breaks and/or alkali labile sites in both transformed and control cells in comet assays. The BCR/ABL -transformed cells needed only 60 min to remove damage to their DNA, whereas controls took 120 min. We hypothesize that this observed increase in the efficacy of repair in BCR/ABL- positive cells is involved in their resistance to idarubicin. Copyright 2002 Academic Press Ltd. All rights reserved.
机译:BCR / ABL致癌酪氨酸激酶负责费城染色体阳性人类白血病的发病机理,并由特定的相互染色体易位t(9; 22)(q34-; q11 +)产生。我们在小鼠pro-B淋巴样细胞系BaF3及其BCR / ABL转化克隆中检查了DNA修复在对伊达比星的治疗药物抗性中的作用。这些细胞可以用作人类白血病的模型。 MTT分析显示,与对照BaF3细胞相比,BCR / ABL转化的细胞显示出对依达比星的抗性在0.3-0.5μm的范围内。在彗星试验中,0.3和1μm的依达比星在转化细胞和对照细胞中均以链断裂和/或碱不稳定位点的形式诱导DNA损伤。 BCR / ABL转化的细胞仅需60分钟即可消除对其DNA的损伤,而对照则需要120分钟。我们假设这种观察到的BCR / ABL阳性细胞修复功效的提高与它们对伊达比星的抗性有关。版权所有2002 Academic Press Ltd.。保留所有权利。

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