title: Chromosomes bearing amplified genes are a preferential target of chemicals inducing chromosome breakage and aneuploidy.
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.
authors.affiliation: Laboratory of Mutagenesis, IST, Genoa, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Ottaggio
authors.forename: S
authors.initials: S
authors.lastname: Bonatti
authors.forename: Z
authors.initials: Z
authors.lastname: Cavalieri
authors.forename: A
authors.initials: A
authors.lastname: Abbondandolo
mesh_terms: D000782:Aneuploidy; D000818:Animals; D001221:Aspartate Carbamoyltransferase / Q000235:genetics; D002223:Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing) / Q000235:genetics; D002330:Carmustine / Q000633:toxicity; D002460:Cell Line; D002869:Chromosome Aberrations; D006224:Cricetinae; D003412:Cricetulus; D004080:Dihydroorotase / Q000235:genetics; D005784:Gene Amplification; D017404:In Situ Hybridization, Fluorescence; D015162:Micronucleus Tests; D009097:Multienzyme Complexes / Q000235:genetics; D016296:Mutagenesis; D014747:Vinblastine / Q000633:toxicity
chemical_list: C033626:CAD trifunctional enzyme; D009097:Multienzyme Complexes; D014747:Vinblastine; D001221:Aspartate Carbamoyltransferase; D004080:Dihydroorotase; D002223:Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing); D002330:Carmustine