Studies on roles of poly (ADP-ribosyl) ation reaction in cell differentiation and programd cell death

(1)聚ADP-核糖合成酶抑制剂的发现：通过对各种天然化合物和治疗药物中合成酶抑制剂的广泛调查，我们发现许多化合物表现出中等程度的抑制作用（IC_<50>= 1 μ M-1 mM）。它们包括通过热解由氨基酸产生的杂环胺，以及香豆素、色酮、磷脂和维司力酮（Arkin-Z）的衍生物<TM>。(2)通过聚（ADP-核糖）抑制剂诱导癌细胞分化：发现苄基维司力农和PhIP（其是食物中丰富的杂环胺）最有效地诱导培养的畸胎癌EC细胞的神经元分化。(3)Poly的变化分化诱导的细胞中的（ADP-核糖）代谢：聚（ADP-核糖）合成被发现在非常早期的阶段瞬时增加这一发现与目前认为的多聚维甲酸的单调失活不同，（ADP-核糖）的合成，提出了一个可能参与的DNA片段化和它的调节聚（ADP-核糖）在细胞分化的起始。

(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.