Kharbanda S M, Miyazaki K, Takeyama H, Sherman M L, Spriggs D R, Carney W P, Kufe D W
Laboratory of Clinical Pharmacology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115.
Cancer Commun. 1989;1(3):191-7.
Tiazofurin (2-beta-D-ribofuranosylthiazole-4-carboxamide, NSC 286193) is a synthetic nucleoside inhibitor of inosine monophosphate dehydrogenase. This agent has recently been shown to induce differentiation of human leukemia cell lines. In the present study, we have monitored the effects of tiazofurin on differentiation and proto-oncogene expression in K562 erythroleukemia cells. Tiazofurin induced K562 cell hemoglobin production in a concentration-dependent manner. This induction of a differentiated phenotype was also associated with a loss of proliferative capacity. In contrast to the reversible effects of hemin on induction of K562 cell hemoglobin synthesis, the effects of tiazofurin were irreversible. Northern blot analysis of K562 cells treated with 10 microM tiazofurin demonstrated the accumulation of alpha- and gamma-globin mRNA. The results also demonstrate that there was little if any effect of tiazofurin on levels of c-myc, c-myb, or c-abl mRNA. Furthermore, there were no detectable changes in Ki-ras, Ha-ras or N-ras expression at the mRNA and protein levels in tiazofurin-treated K562 cells. These findings suggest that tiazofurin induces changes in levels of globin transcripts but has little if any effect on c-myc, c-myb, c-abl, or c-ras gene expression in K562 cells.
硫唑嘌呤（2-β-D-呋喃核糖基噻唑-4-甲酰胺，NSC 286193）是一种肌苷单磷酸脱氢酶的合成核苷抑制剂。最近已证明该药物可诱导人白血病细胞系分化。在本研究中，我们监测了硫唑嘌呤对K562红白血病细胞分化和原癌基因表达的影响。硫唑嘌呤以浓度依赖的方式诱导K562细胞产生血红蛋白。这种分化表型的诱导也与增殖能力的丧失有关。与血红素对K562细胞血红蛋白合成诱导的可逆作用相反，硫唑嘌呤的作用是不可逆的。用10 microM硫唑嘌呤处理的K562细胞的Northern印迹分析表明α-和γ-珠蛋白mRNA的积累。结果还表明，硫唑嘌呤对c-myc、c-myb或c-abl mRNA水平几乎没有影响。此外，在硫唑嘌呤处理的K562细胞中，mRNA和蛋白质水平的Ki-ras、Ha-ras或N-ras表达没有可检测到的变化。这些发现表明，硫唑嘌呤诱导珠蛋白转录本水平的变化，但对K562细胞中的c-myc、c-myb、c-abl或c-ras基因表达几乎没有影响。
