Isolation of Amplified and Overexpressed DNA Sequences from Adriamycin-resistant Human Breast Cancer Cells Academic Article Article uri icon

Overview

MeSH Major

  • Emergency Service, Hospital
  • National Health Programs

abstract

  • 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.

publication date

  • January 1987

Research

keywords

  • Academic Article

Identity

PubMed ID

  • 2441861

Additional Document Info

start page

  • 5092

end page

  • 6

volume

  • 47

number

  • 19