1992 Fiscal Year Final Research Report Summary
Studies on roles of poly(ADP-ribose) in cell differentiation and carcinogenesis
| Project/Area Number |
03454159
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Pathological medical chemistry
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
UEDA Kunihiro Kyoto Univ. Fac. of Med Dept. of Lab. Med. Assoc. Prof., 医学部, 助教授 (00027070)
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| Project Period (FY) |
1991 – 1992
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| Keywords | Poly(ADP-ribose) / Enzyme inhibitor / ADP-ribosyltransferase / Enzyme activator / Cell differentiation / Teratocarcinoma / Vesnarinone / Bloom syndrome |
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| Research Abstract |
1. Inhibitors of ADP-ribosylation: From among >400 organic compounds, we found many strong inhibitors of poly(ADP-ribose) synthetase. Part of them proved to be inhibitory to mono(ADP-ribosyl)transferases.
2. Activators of poly(ADP-ribosyl)ation: We found activation of poly(ADP-ribose) synthetase by metal ions, organic solvents, polyanions, chelators, and carboline compounds.
3. Tumor cell differentiation: We found the action of 4-hydroxyquinazoline and other new inhibitors to induce endothelial differentiation of teratocarcinoma EC cells in culture.
4. Vesnarinone: We found vesnarinone and its derivatives to inhibit poly(ADP-ribose) synthetase and induce EC cell differentiation into neuronal or glial cells.
5. Calcium ion: We found correlation between poly(ADP-ribose) synthetase activity and Ca^<++> concentrations in differentiation-induced epidermal transformed cells.
6. Bloom syndrome: We found an abnormally low activity of poly(ADP-ribose) synthetase in lymphocytes of low-SCE type Bloom syndrome.
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