Induction of chromosomal aberrations (unstable and stable) by inhibitors of topoisomerase II, m-AMSA and VP16, using conventional Giemsa staining and chromosome painting techniques

Mutagenesis. 1998 Jan;13(1):39-43. doi: 10.1093/mutage/13.1.39.

Abstract

Frequencies of symmetrical and asymmetrical exchange aberrations induced by two inhibitors of topoisomerase II, namely, 4'-(9-acridinylamino) methanesulfon-m-anisidide (m-AMSA) and etoposide (VP16), were estimated in human peripheral blood lymphocytes. The aberrations were scored using conventional Giemsa staining and fluorescence in situ hybridization (FISH) techniques, using chromosome-specific DNA libraries. Stable aberrations (translocations) were detected using two cocktails of DNA libraries specific for three chromosomes, namely 1, 3 and X and 2, 4 and 8, representing approximately 40% of the whole human genome. The frequencies of dicentrics and translocations increased in a dose-dependent manner, however, m-AMSA was found to be a more potent inducer of chromosomal aberrations in comparison with VP16 (at concentrations at which comparable frequencies of aberrations were induced) by 20- to 30-fold. When corrected for DNA content of chromosomes in each cocktail, a higher frequency of translocations with the cocktail consisting of chromosomes 2, 4 and 8 in comparison with 1, 3 and X was evident. The genomic translocation frequency calculated from chromosome painting analysis for m-AMSA exceeded that estimated for dicentrics by approximately 2-fold. However, for VP16 almost equal frequencies of both types of chromosome exchange were found.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amsacrine / pharmacology*
  • Azure Stains*
  • Chromosome Aberrations / genetics*
  • Chromosome Banding / methods*
  • Etoposide / pharmacology*
  • Humans
  • Male
  • Staining and Labeling
  • Topoisomerase II Inhibitors*
  • Translocation, Genetic / drug effects

Substances

  • Azure Stains
  • Topoisomerase II Inhibitors
  • Amsacrine
  • Etoposide