| Project/Area Number |
05454169
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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.Inst.for Chem.Res., Professor, 科学研究所, 教授 (00027070)
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| Co-Investigator(Kenkyū-buntansha) |
KIDO Takahiro Kyoto Univ., Col.of Med.Technol., Assist.Prof., 医療技術短期大学部, 助手 (60234308)
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| Project Period (FY) |
1993 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥6,700,000 (Direct Cost: ¥6,700,000)
Fiscal Year 1994: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1993: ¥4,400,000 (Direct Cost: ¥4,400,000)
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| Keywords | Poly (ADP-ribose) / Poly (ADP-ribose) synthetase / Teratocarcinoma EC cells / Induction of cell differentiation / Benzylvesnarinone / Heterocyclic amines / PhIP / Retinoic acid / 阻害剤 / 賦活剤 / ベスナリノン / テラトカルシノーマ細胞 / 分化誘導 / アポトーシス |
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| Research Abstract |
(1) Discovery of poly (ADP-ribose) synthetase inhibitors : From an extensive survey of the synthetase inhibitors among various natural compounds and therapeutic drugs, we found many compounds to exhibit the inhibitory effect to a moderate degree (IC_<50>=1muM-1mM). They include heterocyclic amines produced from amino acids by pyrolysis, and derivatives of coumarine, chromone, phospholipids and vesnarinone (Arkin-Z^<TM>).
(2) Induction of cancer cell differentiation by poly (ADP-ribose) inhibitors : Benzylvesnarinone and PhIP,that is an abundant heterocyclic amine in food, were found to induce most efficiently the neuronal differentiation of teratocarcinoma EC cells in culture.
(3) Changes in poly (ADP-ribose) metabolism in differentiation-induced cells : Poly (ADP-ribose) synthesis was found to increase transiently at the very early stage (within 1 day) of teratocarcinoma EC cell differentiation induced by all-trans-retrinoic acid.This finding, unlike the current view of monotonous inactivation of poly (ADP-ribose) synthesis, suggested a possible involvement of DNA fragmentation and its regulation by poly (ADP-ribose) in the initiation of cell differentiation.
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