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

(1)聚腺苷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>= 1mm - 1mm）。它们包括由氨基酸热解产生的杂环胺，以及香豆素、色素、磷脂和蛇皮苷酮的衍生物（Arkin-Z^<TM>）。(2)聚腺苷核糖（adp -核糖）抑制剂对癌细胞分化的诱导作用：在培养过程中发现，苯基蛇苷酮（Benzylvesnarinone）和食物中丰富的杂环胺PhIP对畸形瘤EC细胞的神经元分化诱导效果最好。(3)分化诱导细胞中poly （adp -核糖）代谢的变化：在全反式缩氨酸诱导的畸胎癌EC细胞分化的极早期（1天内），poly （adp -核糖）合成短暂增加。这一发现不同于目前认为poly （adp -核糖）合成单一失活的观点，表明可能参与了DNA片段化及其由poly （adp -核糖）调控的细胞分化起始过程。

(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.