Ethidium bromide changes the nuclease-sensitive DNA binding sites of the antitumor drug cis-diamminedichloroplatinum(II).

Ethidium bromide changes the nuclease-sensitive DNA binding sites of the antitumor drug cis-diamminedichloroplatinum(II).
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溴化乙锭会改变抗肿瘤药物顺式二氨二氯铂 (II) 的核酸酶敏感 DNA 结合位点。

DOI:
10.1073/pnas.79.11.3489
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发表时间:
1982
影响因子:
11.1
通讯作者:
Lippard,SJ
Lippard,SJ
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Tullius,TD;Lippard,SJ

文献摘要

被引文献

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外切酶III先前已被证明可以揭示抗肿瘤药物顺式二胺二氯铂(II)在DNA上的结合位点。用插入物溴化乙啶预处理相同的DNA,可以通过外切酶III方法检测到新的铂结合位点。特别是,质粒pBR322 165碱基对限制性片段中的5‘d(G6-D-G2)3’序列成为外切酶iii可检测的顺式二胺氯化铂(II)结合的首选位点。在另一种药物——溴化乙啶的影响下,核酸酶敏感铂结合到新位点的转变,在分子水平上为联合化疗中的协同作用现象提供了解释。
Exonuclease III has been shown previously to reveal the binding sites of the antitumor drug cis-diamminedichloroplatinum(II) on DNA. Pretreatment of the same DNA with the intercalator ethidium bromide causes new platinum binding sites to be detected by the exonuclease III method. In particular, a 5'd(G6-D-G2)3' sequence in a 165-base-pair restriction fragment of plasmid pBR322 becomes a preferred site for exonuclease III-detectable cis-diamminedichloroplatinum(II)binding. This switching of nuclease-sensitive platinum binding to new sites by the influence of another drug, ethidium bromide, offers an explantation at the molecular level for the phenomenon of synergism in combination chemotherapy.