Reduced DNA topoisomerase II activity and drug-stimulated DNA cleavage in 9-hydroxyellipticine resistant cells

Biochem Pharmacol. 1988 Jun 1;37(11):2145-9. doi: 10.1016/0006-2952(88)90573-4.


We have isolated a Chinese hamster lung cell line resistant to 9-hydroxyellipticine (DC-3F/9-OH-E) which is also cross-resistant to topoisomerase II inhibitors such as amsacrine and etoposide. In this work we have studied quantitatively both DNA topoisomerase II activity by decatenation of kinetoplast DNA and drug-stimulated DNA cleavage of pBR 322. DNA topoisomerase II activity of DC-3F/9-OH-E nuclear extract was reduced by 3.5-fold as compared to that from DC-3F (sensitive parent) nuclear extract. We also found that DC-3F/9-OH-E nuclear extracts have a reduced capacity to induce in vitro topoisomerase II-mediated DNA cleavage upon stimulation by etoposide and amsacrine (7- and 10-fold respectively). Besides, mixing nuclear extracts from both sensitive and resistant cells indicates that either the enzyme in resistant cells is modified or a modulating factor is associated to it. Our results suggest that the resistance of the DC-3F/9-OH-E cell line to topoisomerase II inhibitors might be due to both a reduced amount of the enzyme and its reduced ability to form the cleavable complex in the presence of drugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / pharmacology*
  • Amsacrine / pharmacology
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Cells, Cultured
  • Cricetinae
  • Cricetulus
  • DNA / drug effects*
  • Drug Resistance
  • Ellipticines / pharmacology*
  • Podophyllotoxin / pharmacology
  • Topoisomerase II Inhibitors*


  • Alkaloids
  • Antineoplastic Agents
  • Ellipticines
  • Topoisomerase II Inhibitors
  • Amsacrine
  • DNA
  • 9-hydroxyellipticine
  • Podophyllotoxin