Induction of murine teratocarcinoma cell differentiation by suppression of poly(ADP-ribose) synthesis.
Induction of murine teratocarcinoma cell differentiation by suppression of poly(ADP-ribose) synthesis.
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通过抑制聚（ADP-核糖）合成诱导小鼠畸胎癌细胞分化。
DOI：
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发表时间：
1984
影响因子：
11.1
通讯作者：
O. Niwa
中科院分区：
文献类型：
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作者：
Y. Ohashi;K. Ueda;O. Hayaishi;K. Ikai;O. Niwa
小鼠畸胎癌EC-A1细胞在维甲酸诱导分化过程中聚ADP-核糖合成活性明显下降，在透性化细胞中加入0.1 μ M维甲酸后2天和3天，聚ADP-核糖合成活性分别降至对照（未诱导细胞）的25%和10%。这种变化先于形态学和DNA合成的变化，4天后变得突出。聚（ADP-核糖）合成活性的降低似乎是由合成酶蛋白的减少引起的，而不是由其催化活性的降低引起的，因为DNA酶I处理所公开的全部活性平行地降低，尽管是在约20倍高的水平。当向培养基中加入聚（ADP-核糖）合成酶的特异性抑制剂8 mM 3-氨基苯甲酰胺或10 mM烟酰胺时，细胞在7-9天后经历分化。类似物，3-氨基苯甲酸，这是不抑制的合成酶，诱导分化的效率比3-氨基苯甲酰胺低得多，和3-氨基苯甲酸的效果似乎是归因于其强大的细胞毒性。使用抗聚（ADP-核糖）抗体的免疫组织化学分析证实，在用视黄酸或3-氨基苯甲酰胺处理的细胞核中聚（ADP-核糖）合成活性显著降低，但用3-氨基苯甲酸处理的细胞核中聚（ADP-核糖）合成活性不显著降低。这些结果表明，聚（ADP-核糖）合成的减少触发畸胎瘤细胞的分化。
Poly(ADP-ribose) synthesizing activity in mouse teratocarcinoma EC-A1 cells decreased markedly during differentiation induced by retinoic acid; the activities assayed in permeabilized cells decreased to 25% and 10% of the activity of control (uninduced cells) 2 and 3 days, respectively, after the addition of 0.1 microM retinoic acid to the culture medium. This change preceded changes in morphology and DNA synthesis, which became prominent after 4 days. The decrease in poly(ADP-ribose) synthesizing activity appeared to be caused by a diminution of the synthetase protein and not by a decrease in its catalytic activity, because the full activity disclosed by DNase I treatment decreased in parallel, albeit at about 20 times higher levels. When 8 mM 3-aminobenzamide or 10 mM nicotinamide, specific inhibitors of poly(ADP-ribose) synthetase, was added to the culture medium, the cells underwent differentiation after 7-9 days. An analogue, 3-aminobenzoic acid, which is not inhibitory to the synthetase, induced differentiation much less efficiently than did 3-aminobenzamide, and the effect of 3-aminobenzoic acid appeared to be ascribable to its potent cytotoxicity. Immunohistochemical analysis using anti-poly(ADP-ribose) antibody confirmed the marked reduction in poly(ADP-ribose) synthesizing activity in nuclei of the cells treated with retinoic acid or 3-aminobenzamide but not with 3-aminobenzoic acid. These results suggest that a decrease in poly(ADP-ribose) synthesis triggers differentiation of teratocarcinoma cells.