Darmon M, Nicolas J F, Lamblin D
EMBO J. 1984 May;3(5):961-7. doi: 10.1002/j.1460-2075.1984.tb01914.x.
The inhibitor of DNA-methylation, 5-azacytidine (5- AzaC ) induced the appearance of cytokeratin-containing cells in several mesenchymal cell lines such as teratocarcinoma-derived fibroblasts, preadipocytes and myoblasts, NIH-3T3 fibroblasts and human embryonic fibroblasts. At optimal 5- AzaC concentrations the proportion of such cells was in the range of 10(-1) compared with 10(-6) -10(-4) in non-treated cultures. Dose-response curves indicated that the induction of cytokeratin was the result of an interaction of the drug with few targets. Stable, mature, keratinocyte cell lines, as well as lines of myoblasts and astrocytes, could be isolated from a teratocarcinoma-derived preadipocyte line, showing that 5- AzaC is able to provoke a wide range of complete phenotypic conversions. In these cell lines, the intermediate filaments corresponded to the morphological phenotype. Altogether, the results suggest that 5- AzaC preferentially activates certain genes.
DNA甲基化抑制剂5-氮杂胞苷(5-AzaC)可诱导几种间充质细胞系中出现含细胞角蛋白的细胞,如畸胎瘤衍生的成纤维细胞、前脂肪细胞和成肌细胞、NIH-3T3成纤维细胞以及人胚胎成纤维细胞。在最佳5-AzaC浓度下,此类细胞的比例为10(-1),而未处理培养物中的比例为10(-6)-10(-4)。剂量反应曲线表明,细胞角蛋白的诱导是药物与少数靶点相互作用的结果。可以从畸胎瘤衍生的前脂肪细胞系中分离出稳定、成熟的角质形成细胞系以及成肌细胞和星形胶质细胞系,这表明5-AzaC能够引发广泛的完全表型转化。在这些细胞系中,中间丝与形态学表型相对应。总之,结果表明5-AzaC优先激活某些基因。