Formation of blocking lesions at identical DNA sequences by the nitrosourea and platinum classes of anticancer drugs.
Formation of blocking lesions at identical DNA sequences by the nitrosourea and platinum classes of anticancer drugs.
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发表时间：
1987-10
期刊：
影响因子：
11.2
通讯作者：
J. Gralla;S. Sasse-Dwight;L. Poljak
中科院分区：
文献类型：
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作者：
J. Gralla;S. Sasse-Dwight;L. Poljak
顺式二胺二氯铂（II）（顺铂）化合物和氯乙基亚硝基源是两种不同类型的抗癌药物，它们通过修饰DNA共价起作用。我们将铂化药物顺铂与烷基化药物双氯乙基亚硝基脲和其他氯乙基亚硝基脲进行了比较，方法是在体外修饰双链DNA，并发现阻碍大肠杆菌DNA聚合酶进展的阻断性病变。尽管顺铂和氯乙基亚硝基源的结构和反应性非常不同，但它们在相同的DNA链上含有相邻的鸟苷，它们的原发阻断病变的序列相同。在肿瘤病毒SV 40 DNA中，这两种药物的一个非常强的靶点是调控序列ggggcgg，该序列重复6次，是病毒复制的重要序列，也是病毒转化基因表达的必需序列。已知与这些GC盒元件相关的序列存在于许多逆转录病毒和癌基因的侧翼区域，从而提高了靶向肿瘤细胞中这些序列有助于药物活性的可能性。
cis-Diamminedichloroplatinum (II) (cisplatin) compounds and the chloroethylnitrosoureas are two different classes of anticancer drugs that work by modifying DNA covalently. We have compared the platinating drug cisplatin with the alkylating drug bischloroethylnitrosourea and other chloroethylnitrosoureas by modifying double stranded DNA in vitro and identifying blocking lesions that impede the progress of Escherichia coli DNA polymerase. Despite their very different structures and reactivities, cisplatin and the chloroethylnitrosoureas from primary blocking lesions at identical sequences, those containing adjacent guanosines on the same DNA strand. In tumor virus SV 40 DNA, a very strong target for both types of drugs is the regulatory sequence GGGCGG, which is repeated six times and is an important sequence for viral replication and an essential sequence for expression of the viral transforming gene. Sequences related to these GC box elements are known to be present in the flanking regions of many retroviruses and oncogenes, thus raising the possibility that the targeting of these sequences in tumor cells contributes to drug activity.