Does the BCR/ABL-mediated increase in the efficacy of DNA repair play a role in the drug resistance of cancer cells?
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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DOI：
10.1006/cbir.2002.0865
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发表时间：
2002-01-01
影响因子：
3.9
通讯作者：
Skórski, T
中科院分区：
文献类型：
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作者：
Majsterek, I;Blasiak, J;Skórski, T
BCR/ABL致癌性酪氨酸激酶与费城染色体阳性人白血病的发病机制有关，由特异性的染色体易位t(9;22)（q34 -;q11 +）产生。我们研究了DNA修复在小鼠前b淋巴样细胞系BaF3及其BCR/ abl转化克隆对伊达柔比星治疗性耐药中的作用。这些细胞可以用作人类白血病的模型。MTT实验显示，与对照BaF3细胞相比，BCR/ abl转化的细胞在0.3-0.5 muM范围内对伊达柔比星表现出耐药性。在彗星试验中，0.3和1mum的伊达柔比星在转化细胞和对照细胞中以链断裂和/或碱不稳定位点的形式诱导DNA损伤。BCR/ abl转化的细胞只需要60分钟就能消除DNA损伤，而对照组则需要120分钟。我们推测，在BCR/ abl阳性细胞中观察到的修复效果的增加与它们对伊达柔比星的耐药性有关。(C) 2002学术出版社有限公司版权所有。
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 muM, compared with the control BaF3 cells. Idarubicin at 0.3 and 1 muM 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. (C) 2002 Academic Press Ltd. All rights reserved.