title: Duplicated chromosomal fragments stabilize shortened telomeres in normal human IMR-90 cells before transition to senescence.
abstract: To assess why during in vitro aging of fibroblasts the maintenance of chromosomal stability is effective or occasionally fails, a detailed cytogenetic analysis was performed in normal human IMR-90 fetal lung fibroblasts. The onset of senescence was inferred from proliferation activity, expression pattern of cell cycle regulating proteins, activity of β-galactosidase, and morphological features. Over the period of proliferation, a moderate increase of non-transmissible structural chromosomal aberrations was observed. In addition, using fluorescence in situ hybridization (mFISH and mBAND) techniques, we detected clonally expanding translocations in up to 70% of the analyzed metaphases, all involving one homolog of chromosome 9 as an acceptor. Notably, chromosomes are randomly involved as donor-chromosomes of the translocated terminal acentric fragments. These fragments result from duplication because the donor chromosomes are apparently unchanged. Interstitial telomeric signals were detectable at fusion sites, most likely belonging to chromosome 9. Quantitative fluorescence in situ hybridization (QFISH) detecting telomere sequences, followed by mFISH technique revealed that already in young cells the respective telomeres of one chromosome 9 were particularly short. For the first time, we have observed dysfunctional telomeres of one specific chromosome in normal human cells that have been stabilized by duplicated terminal sequences.
authors: Biophysics Department, GSI Helmholtz Center for Heavy Ion Research, Darmstadt, Germany.
authors: Sebastian
authors: S
authors: Zahnreich
authors: Damir
authors: D
authors: Krunic
authors: Larissa
authors: L
authors: Melnikova
authors: Agnes
authors: A
authors: Szejka
authors: Barbara
authors: B
authors: Drossel
authors: Laure
authors: L
authors: Sabatier
authors: Marco
authors: M
authors: Durante
authors: Sylvia
authors: S
authors: Ritter
authors: Claudia
authors: C
authors: Fournier
mesh_terms: D002460:Cell Line; D016922:Cellular Senescence / Q000502:physiology*; D058674:Chromosome Duplication; D002877:Chromosomes, Human / Q000378:metabolism*; D020732:Cytogenetic Analysis; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D016615:Telomere / Q000378:metabolism*