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

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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.