INCREASED POLY(ADP-RIBOSYL)ATION IN INTACT-CELLS BY CISPLATIN TREATMENT

INCREASED POLY(ADP-RIBOSYL)ATION IN INTACT-CELLS BY CISPLATIN TREATMENT
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DOI:
10.1093/carcin/14.4.559
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发表时间:
1993-04-01
期刊:
影响因子:
4.7
通讯作者:
ZELLER, WJ
ZELLER, WJ
中科院分区:
医学2区
文献类型:
--
作者:
BURKLE, A;CHEN, G;ZELLER, WJ

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顺铂(DDP)是临床重要的抗肿瘤药物,可诱导DNA - DNA和DNA -蛋白质形成交联。我们已经研究了DDP处理细胞培养后是否会诱导聚(adp -核糖基)化,这是一种核蛋白的翻译后修饰,由于DNA链断裂的存在而急剧增加,并在DNA修复中起作用。利用免疫荧光技术原位检测完整细胞中的聚(adp -核糖),我们发现DDP处理0-342大鼠卵巢肿瘤细胞或CV-1猴细胞后出现斑点性核信号,而未处理的对照细胞和adp -核糖基化抑制剂3-氨基苯甲酰胺孵育后的DDP处理细胞均无斑点性核信号。因此,我们的结果为细胞对DDP治疗的反应中poly(ADP-ribosyl)化的参与提供了直接证据,更一般地说,说明了这种快速原位检测活细胞中poly(ADP-ribosyl)化增加的多功能性。
Cisplatin (DDP) is a clinically important antitumor drug that induces the formation of DNA - DNA and DNA - protein crosslinks. We have studied whether poly(ADP-ribosyl)ation, a post-translational modification of nuclear proteins that is drastically increased by the presence of DNA strand breaks and plays a role in DNA repair, is induced following DDP treatment of cell cultures. By using an immunofluorescence technique for the in situ detection of poly(ADP-ribose) in intact cells, we found spotty nuclear signals after DDP treatment of 0-342 rat ovarian tumor cells or CV-1 monkey cells, but not in untreated control celts, nor in DDP-treated cells postincubated with the ADP-ribosylation inhibitor 3-aminobenzamide. Our results thus provide direct evidence for an involvement of poly(ADP-ribosyl)ation in the cell's response to DDP treatment and, more generally, illustrate the versatility of this rapid in situ method for the detection of increased poly(ADP-ribosyl)ation in living cells.