Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
Original Research Article
Duplicated chromosomal fragments stabilize shortened telomeres in normal human IMR-90 cells before transition to senescence†
Article first published online: 23 JAN 2012
Copyright © 2011 Wiley Periodicals, Inc.
Journal of Cellular Physiology
Volume 227, Issue 5, pages 1932–1940, May 2012
How to Cite
Zahnreich, S., Krunic, D., Melnikova, L., Szejka, A., Drossel, B., Sabatier, L., Durante, M., Ritter, S. and Fournier, C. (2012), Duplicated chromosomal fragments stabilize shortened telomeres in normal human IMR-90 cells before transition to senescence. J. Cell. Physiol., 227: 1932–1940. doi: 10.1002/jcp.22921
- Issue published online: 23 JAN 2012
- Article first published online: 23 JAN 2012
- Accepted manuscript online: 5 JUL 2011 10:28AM EST
- Manuscript Accepted: 21 JUN 2011
- Manuscript Received: 15 MAR 2011
- German Federal Ministry of Education and Research (BMBF). Grant Number: 02 S 849
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. J. Cell. Physiol. 227: 1932–1940, 2012. © 2011 Wiley Periodicals, Inc.