Studies on the role of poly(ADP-ribose) in cell differentiation and oncogenesis

1.多聚腺苷二磷酸核糖合成活性在细胞分化过程中的变化分析：髓细胞成熟过程中合成酶活性的消失在许多髓系白血病病例中得到证实。发现和分析新的聚腺苷二磷酸核糖合成酶抑制剂：通过对200多个化合物的调查，发现了许多新的有效的合成酶抑制剂，包括已知抑制剂的类似物和完全不同化学结构的衍生物。并研究了这些抑制剂的构效关系。抑制聚(ADP-核糖)合成诱导癌细胞分化：4-羟基喹唑啉是一种新型合成酶抑制剂，具有诱导畸胎癌细胞分化的作用。显微注射技术分析：将抗多聚(ADP-核糖)抗体显微注射入Friend的红白血病细胞中，不能诱导其向产生血红蛋白的细胞分化。分化相关基因表达变化分析：在大鼠睾丸中观察到精子发生过程中聚(ADP-核糖)合成酶的逐渐消失。其他分析：对谷氨酰核糖-5-磷酸贮藏病和聚腺苷二磷酸-核糖合成酶的cDNA进行了研究。

1. Analysis of changes in poly(ADP-ribose) synthesizing activity during cell differentiation: Disappearance of the synthetase activity during maturation of myelocytes was confirmed with many cases of myelogenous leukemia.2. Discovery and analysis of new inhibitors of poly(ADP-ribose) synthetase: By a survey of more than 200 compounds, many new and potent inhibitors of the synthetase were discovered, including analogues of known inhibitors and derivatives of completely different chemical structures. A structure-activity relationship of these inhibitors was also studied.3. Induction of cancer cell differentiation by suppression of poly(ADP-ribose) synthesis: One of the new inhibitors of synthetase, i.e. 4-hydroxyquinazoline, was shown to induce differentiation of teratocarcinoma cells.4. Analysis with microinjection technique: Microinjection of anti-poly(ADP-ribose) antibody into Friend's erythroleukemia cells failed to induce differentiation to hemoglobin-producing cells.5. Analysis of differentiation-associated changes in gene expression: Progressive disappearance of poly(ADP-ribose) synthetase during spermatogenesis was observed in rat testis.6. Other analysis: Studies on glutamyl ribose-5-phosphate storage disease and on cDNA for poly(ADP-ribose) synthetase were also carried out.