PMID- 8698806
OWN - NLM
STAT- MEDLINE
DCOM- 19960903
LR  - 20190508
IS  - 0021-9525 (Print)
IS  - 1540-8140 (Electronic)
IS  - 0021-9525 (Linking)
VI  - 134
IP  - 1
DP  - 1996 Jul
TI  - In situ analysis of changes in telomere size during replicative aging and cell 
      transformation.
PG  - 1-12
AB  - Telomeres have been shown to gradually shorten during replicative aging in human 
      somatic cells by Southern analysis. This study examines telomere shortening at 
      the single cell level by fluorescence in situ hybridization (FISH). FISH and 
      confocal microscopy of interphase human diploid fibroblasts (HDFs) demonstrate 
      that telomeres are distributed throughout the nucleus with an interchromosomal 
      heterogeneity in size. Analysis of HDFs at increasing population doubling levels 
      shows a gradual decrease in spot size, intensity, and detectability of telomeric 
      signal. FISH of metaphase chromosomes prepared from young and old HDFs shows a 
      heterogeneity in detection frequency for telomeres on chromosomes 1, 9, 15, and 
      Y. The interchromosomal distribution of detection frequencies was similar for 
      cells at early and late passage. The telomeric detection frequency for metaphase 
      chromosomes also decreased with age. These observations suggest that telomeres 
      shorten at similar rates in normal human somatic cels. T-antigen transformed HDFs 
      near crisis contained telomere signals that were low compared to nontransformed 
      HDFs. A large intracellular heterogeneity in telomere lengths was detected in two 
      telomerase-negative cell lines compared to normal somatic cells and the 
      telomerase-positive 293 cell line. Many telomerase-negative immortal cells had 
      telomeric signals stronger than those in young HDFs, suggesting a different 
      mechanism for telomere length regulation in telomerase-negative immortal cells. 
      These studies provide an in situ demonstration of interchromosomal heterogeneity 
      in telomere lengths. Furthermore, FISH is a reliable and sensitive method for 
      detecting changes in telomere size at the single cell level.
FAU - Henderson, S
AU  - Henderson S
AD  - Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
FAU - Allsopp, R
AU  - Allsopp R
FAU - Spector, D
AU  - Spector D
FAU - Wang, S S
AU  - Wang SS
FAU - Harley, C
AU  - Harley C
LA  - eng
GR  - AG-09383/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Cell Biol
JT  - The Journal of cell biology
JID - 0375356
SB  - IM
MH  - Cell Division
MH  - *Cell Transformation, Viral
MH  - Cells, Cultured
MH  - *Cellular Senescence
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Simian virus 40
MH  - Telomere/*ultrastructure
PMC - PMC2120915
EDAT- 1996/07/01 00:00
MHDA- 1996/07/01 00:01
PMCR- 1997/01/01
CRDT- 1996/07/01 00:00
PHST- 1996/07/01 00:00 [pubmed]
PHST- 1996/07/01 00:01 [medline]
PHST- 1996/07/01 00:00 [entrez]
PHST- 1997/01/01 00:00 [pmc-release]
AID - 96293346 [pii]
AID - 10.1083/jcb.134.1.1 [doi]
PST - ppublish
SO  - J Cell Biol. 1996 Jul;134(1):1-12. doi: 10.1083/jcb.134.1.1.