Development and characterization of a melphalan-resistant human multiple myeloma cell line.
Development and characterization of a melphalan-resistant human multiple myeloma cell line.
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发表时间：
1991-02
期刊：
影响因子：
11.2
通讯作者：
W. Bellamy;W. Dalton;Mary C. Gleason;T. Grogan;J. Trent
中科院分区：
文献类型：
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作者：
W. Bellamy;W. Dalton;Mary C. Gleason;T. Grogan;J. Trent
我们提供的数据描述了一个人骨髓瘤细胞系(8226/LR-5)，它对马法兰表现出7倍的抗药性，并对其他双功能烷化剂和X射线具有部分交叉抗药性。马法兰耐药性相对不稳定，在没有药物的情况下，耐药性在17周内下降。在该细胞系中观察到的耐药性不是通过减少细胞内的马法兰积聚来调节的。在抗性亚系中，当细胞内药物积累量相等时，DNA链间交联性显著减少。这种减少是由于病变形成的减少，还是由于病变切除速度的增加，仍有待确定。敏感和耐药细胞株的生长特性和细胞周期动力学特征相似，包括S期。在耐药的8226/LR-5细胞中，发现细胞内非蛋白硫醇显著升高；随着细胞恢复或失去耐药性，细胞内非蛋白巯基水平下降。在敏感和耐药细胞系中，预先用丁硫氨酸亚磺胺处理细胞可显著降低非蛋白巯基水平，并增强马法兰的细胞毒性。硫醇似乎在介导马法兰抗性方面发挥了作用。
We present data describing a human myeloma cell line (8226/LR-5) selected for resistance to melphalan which exhibits a 7-fold level of resistance to melphalan and is partially cross-resistant to other bifunctional alkylators and X-irradiation. Melphalan resistance is relatively unstable with a decrease in resistance observed within 17 weeks in the absence of drug. The resistance observed in this cell line is not mediated by reduced intracellular melphalan accumulation. DNA interstrand cross-linking at equivalent intracellular drug accumulation is significantly reduced in the resistant subline. Whether this reduction is the result of a decrease in the formation of this lesion or to an increased rate of removal of the lesion remains to be determined. Growth characteristics and cell cycle kinetics, including S phase, were similar between sensitive and resistant cell lines. Intracellular nonprotein thiols were found to be significantly elevated in the resistant 8226/LR-5 cells; as cells revert or lose resistance, intracellular nonprotein sulfhydryl levels decline. Prior treatment of the cells with buthionine sulfoximine significantly reduced nonprotein sulfhydryl levels and enhanced melphalan cytotoxicity in both the sensitive and resistant cell lines. Thiols appear to play a role in mediating melphalan resistance.