Gusella J F, Housman D
Cell. 1976 Jun;8(2):263-9. doi: 10.1016/0092-8674(76)90010-6.
The effectiveness of purines and purine analogues as inducers of erythroid differentiation in cultured murine erythroleukemia cells has been investigated. These cell lines have previously been shown to differentiate in vitro in response to dimethylsulfoxide (DMSO) and a number of other polar solvents. Two purine analogues, 6-thioguanine and 6-mercaptopurine, as well as the naturally occuring purine, purine, hypoxanthine, are shown to be extremely potent inducers. 6-Thioguanine is effective at a concentration of 0.06 mM, 750 fold lower than the DMSO concentration required for equivalent induction. 6-Mercaptopurine and hypoxanthine are effective inducers at a concentration of approximately 2 mM. Accumulation of globin mRNA was monitored during induction with purine inducers and shown to be similar in amount to globin mRNA levels reached in DMSO-induced cultures. Induction of differentiation by all three compounds follows a similar time course to induction with DMSO. All three compounds are potent inducers of HGPRT (hypoxanthine-guanine phosphoribosyltransferase)-negative cell lines; hence incorporation of purines into DNA is not required for induction of differentiation. Comparison of these compounds with other purines and purine analogues suggests a high degree of specificity in their interaction with a cellular target.
研究了嘌呤及嘌呤类似物在培养的小鼠红白血病细胞中作为红系分化诱导剂的有效性。这些细胞系先前已被证明在体外可对二甲亚砜（DMSO）及其他一些极性溶剂作出分化反应。两种嘌呤类似物，6-硫鸟嘌呤和6-巯基嘌呤，以及天然存在的嘌呤、次黄嘌呤，均显示为极强的诱导剂。6-硫鸟嘌呤在浓度为0.06 mM时有效，比同等诱导所需的DMSO浓度低750倍。6-巯基嘌呤和次黄嘌呤在浓度约为2 mM时是有效的诱导剂。在用嘌呤诱导剂诱导过程中监测了珠蛋白mRNA的积累，结果显示其数量与DMSO诱导培养物中达到的珠蛋白mRNA水平相似。这三种化合物诱导分化的过程与DMSO诱导的过程具有相似的时间进程。这三种化合物都是次黄嘌呤-鸟嘌呤磷酸核糖转移酶（HGPRT）阴性细胞系的有效诱导剂；因此，诱导分化不需要将嘌呤掺入DNA。将这些化合物与其他嘌呤及嘌呤类似物进行比较表明，它们与细胞靶点的相互作用具有高度特异性。
