Hjertner O, Börset M, Waage A
Institute of Cancer Research and Molecular Biology, University of Trondheim, Norway.
Leuk Res. 1996 Feb;20(2):155-60. doi: 10.1016/0145-2126(95)00128-x.
We have studied the effects of 2-chlorodeoxyadenosine (2-CdA) and melphalan on DNA synthesis and cell proliferation of five myeloma cell lines and one primary culture of highly purified myeloma cells. The DNA synthesis was estimated by thymidine incorporation and cell death was estimated by a coluorimetric assay sensitive to mitochondrial activity. The concentrations of 2-CdA giving 50% inhibition of DNA synthesis (ID50) in four cell lines were 8, 100, 500 and 2500 nM, whereas the corresponding concentrations of melphalan were 600, 600, 1000 and 7500 nM, respectively. In one cell line, the ID50 for melphalan was 400 nM, whereas 2-CdA apparently was without inhibitory effect and the ID50 was not reached. The ID50 for 2-CdA in the primary culture was 250 nM. When compared on a molar basis, 2-CdA had a more potent inhibitory effect than melphalan on four out of five myeloma cell lines. This is in contrast to clinical experiments which have shown lack of effect of 2-CdA in myeloma patients. Our study shows that 2-CdA has a marked heterogeneous effect on myeloma cell lines and opens up the possibility that a similar variation in sensitivity may also exist among myeloma cell clones in vivo.
我们研究了2-氯脱氧腺苷（2-CdA）和美法仑对五种骨髓瘤细胞系以及一种高度纯化的骨髓瘤细胞原代培养物的DNA合成和细胞增殖的影响。通过胸腺嘧啶核苷掺入法评估DNA合成，通过对线粒体活性敏感的比色测定法评估细胞死亡。在四种细胞系中，导致DNA合成50%抑制（ID50）的2-CdA浓度分别为8、100、500和2500 nM，而美法仑的相应浓度分别为600、600、1000和7500 nM。在一种细胞系中，美法仑的ID50为400 nM，而2-CdA显然没有抑制作用，未达到ID50。原代培养物中2-CdA的ID50为250 nM。以摩尔为基础进行比较时，2-CdA对五种骨髓瘤细胞系中的四种具有比美法仑更强的抑制作用。这与临床实验结果相反，临床实验表明2-CdA对骨髓瘤患者无效。我们的研究表明，2-CdA对骨髓瘤细胞系具有显著的异质性影响，并揭示了体内骨髓瘤细胞克隆之间可能也存在类似的敏感性差异。
