Chromosomes bearing amplified genes are a preferential target of chemicals inducing chromosome breakage and aneuploidy

Mutat Res. 1993 Mar;301(3):149-55. doi: 10.1016/0165-7992(93)90071-3.

Abstract

Micronuclei were induced in V79 Chinese hamster cells and in PALA L and MTX M, two derivative cell lines harboring amplified genes, with 1,3-bis(2-chloroethyl)nitrosourea (BCNU) and vinblastine. Spontaneous and induced micronuclei were analyzed for the presence of centromeres by immunofluorescent CREST staining. Micronuclei formed in PALA L cells were also analyzed for the presence of amplified DNA by in situ hybridization with a CAD gene probe. Both cell lines containing amplified genes showed increased micronucleus induction by BCNU and vinblastine. The marker chromosome of PALA L cells was found to be a preferential target for both the clastogenic and the aneugenic action of the two chemicals. DNA amplification seems therefore to be a destabilizing factor of chromosomal structural integrity and mitotic segregation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aneuploidy
  • Animals
  • Aspartate Carbamoyltransferase / genetics
  • Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing) / genetics
  • Carmustine / toxicity
  • Cell Line
  • Chromosome Aberrations*
  • Cricetinae
  • Cricetulus
  • Dihydroorotase / genetics
  • Gene Amplification*
  • In Situ Hybridization, Fluorescence
  • Micronucleus Tests
  • Multienzyme Complexes / genetics
  • Mutagenesis*
  • Vinblastine / toxicity

Substances

  • CAD trifunctional enzyme
  • Multienzyme Complexes
  • Vinblastine
  • Aspartate Carbamoyltransferase
  • Dihydroorotase
  • Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing)
  • Carmustine