Sister-chromatid exchanges, chromosomal aberrations and cytotoxicity produced by topoisomerase II-targeted drugs in sensitive (A2780) and resistant (A2780-DX3) human ovarian cancer cells: correlations with the formation of DNA double-strand breaks

Mutat Res. 1994 Nov 1;311(1):21-9. doi: 10.1016/0027-5107(94)90069-8.

Abstract

Doxorubicin, ellipticine and etoposide are antineoplastic drugs with topoisomerase II inhibitory activity. The relationship between drug-induced sister-chromatid exchanges (SCEs) or chromosomal aberrations (CAs) and cytotoxicity, or drug-induced DNA double-strand breaks (DSBs) and cytotoxicity, or drug-induced SCEs and DSBs was investigated in human ovarian cancer cells sensitive (A2780) and resistant (A2780-DX3) to topoisomerase II inhibitors. 30-min drug treatments produced SCEs, CAs and DSBs in sensitive cells, doxorubicin being more potent than etoposide at equimolar concentrations. The same treatments of resistant (A2780-DX3) cells did not produce chromosomal damage (SCEs, CAs, DSBs) and no cytotoxicity was observed. A plot of cytotoxicity versus SCEs indicated a good correlation between these two parameters for topoisomerase II inhibitors and not for mytomicin C. The plot of DSBs versus SCEs also showed a very good correlation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Cell Survival / drug effects
  • Chromosome Aberrations*
  • DNA Damage*
  • DNA, Neoplasm / drug effects
  • Doxorubicin / pharmacology
  • Drug Resistance, Multiple
  • Etoposide / pharmacology
  • Female
  • Humans
  • Mitomycin / pharmacology
  • Ovarian Neoplasms
  • Sister Chromatid Exchange*
  • Topoisomerase II Inhibitors*
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • DNA, Neoplasm
  • Topoisomerase II Inhibitors
  • Mitomycin
  • Etoposide
  • Doxorubicin