DNA Unwinding and Inhibition of Mouse Leukemia L1210 DNA Topoisomerase I by Intercalators

Nucleic Acids Res. 1987 Aug 25;15(16):6713-31. doi: 10.1093/nar/15.16.6713.


The DNA unwinding effects of some 9-aminoacridine derivatives were compared under reaction conditions that could be used to study drug-induced topoisomerase II inhibition. An assay was designed to determine drug-induced DNA unwinding by using L1210 topoisomerase I. 9-aminoacridines could be ranked by decreasing unwinding potency: compound C greater than or equal to 9-aminoacridine greater than o-AMSA greater than or equal to compound A greater than compound B greater than m-AMSA. Ethidium bromide was more potent than any of the 9-aminoacridines. This assay is a fast and simple method to compare DNA unwinding effects of intercalators. It led to the definition of a drug intrinsic unwinding constant (k). An additional finding was that all 9-aminoacridines and ethidium bromide inhibited L1210 topoisomerase I. Enzyme inhibition was detectable at low enzyme concentrations (less than or equal to 1 unit) and when the kinetics of topoisomerase I-mediated DNA relaxation was studied. Topoisomerase I inhibition was not associated with DNA swivelling or cleavage.

Publication types

  • Comparative Study

MeSH terms

  • Aminacrine / analogs & derivatives
  • Aminacrine / pharmacology*
  • Aminoacridines / pharmacology*
  • Animals
  • DNA, Viral / drug effects
  • Ethidium / pharmacology
  • Intercalating Agents / pharmacology*
  • Leukemia L1210 / enzymology*
  • Mice
  • Neoplasm Proteins / antagonists & inhibitors
  • Nucleic Acid Conformation / drug effects
  • Structure-Activity Relationship
  • Topoisomerase I Inhibitors*


  • Aminoacridines
  • DNA, Viral
  • Intercalating Agents
  • Neoplasm Proteins
  • Topoisomerase I Inhibitors
  • Aminacrine
  • Ethidium