PMID- 7679929
OWN - NLM
STAT- MEDLINE
DCOM- 19930331
LR  - 20190512
IS  - 0960-7722 (Print)
IS  - 0960-7722 (Linking)
VI  - 26
IP  - 1
DP  - 1993 Jan
TI  - Induction of replicative senescence by 5-azacytidine: fundamental cell kinetic 
      differences between human diploid fibroblasts and NIH-3T3 cells.
PG  - 45-54
AB  - To analyse the putative role of methylation of cytosine residues in the nuclear 
      DNA as a regulatory step during cellular ageing, we incubated ageing human 
      amniotic fluid derived fibroblast-like cells and non-ageing NIH-3T3 cells with 
      5-azacytidine. BrdUrd/Hoechst and acridine orange (AO) flow cytometry was used to 
      compare the effects of the base analogue on cell proliferation and cell 
      differentiation. In NIH-3T3 cultures, 96h exposures to 4 microM 5-azacytidine 
      caused diminished cell proliferation due to cell arrest in the G1 compartments of 
      the second and third cell cycles of serum stimulated cells. The exit from the 
      G0/G1 compartment was not affected. The 5-azacytidine induced cell kinetic 
      disturbances were unstable in NIH-3T3 cultures, such that pre-treated cells 
      reverted to normal cell cycle transit within 2-3 days after termination of 
      treatment. In contrast, 5-azacytidine pre-treated amniotic fluid derived 
      fibroblast-like cell cultures showed persistently elevated G2 phase arrests and 
      delayed G0/G1 phase exit kinetics, which explain the premature cessation of 
      proliferation observed in these primary cultures. In both cell systems, 
      5-azacytidine exposed cultures showed elevated numbers of G1 phase cells with 
      increased RNA content as revealed by AO flow cytometry. Again, this effect was 
      reversible in NIH-3T3 cells but not in amniotic fluid derived fibroblast-like 
      cells. These contrasting responses to 5-azacytidine are likely to reflect 
      intrinsic differences in methylation patterns or de novo methylase activity 
      between ageing cell strains and non-ageing cell lines.
FAU - Weller, E M
AU  - Weller EM
AD  - Department of Human Genetics, University of Wurzburg, Germany.
FAU - Poot, M
AU  - Poot M
FAU - Hoehn, H
AU  - Hoehn H
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - England
TA  - Cell Prolif
JT  - Cell proliferation
JID - 9105195
RN  - 63231-63-0 (RNA)
RN  - F30N4O6XVV (Acridine Orange)
RN  - G34N38R2N1 (Bromodeoxyuridine)
RN  - M801H13NRU (Azacitidine)
SB  - IM
MH  - 3T3 Cells/drug effects
MH  - Acridine Orange
MH  - Amniotic Fluid/cytology
MH  - Animals
MH  - Azacitidine/*pharmacology
MH  - Bromodeoxyuridine
MH  - Cell Division/*drug effects
MH  - Cell Separation
MH  - Cells, Cultured/drug effects
MH  - Cellular Senescence/drug effects
MH  - Flow Cytometry
MH  - G1 Phase/*drug effects
MH  - G2 Phase/*drug effects
MH  - Humans
MH  - Methylation
MH  - Mice
MH  - RNA/analysis
EDAT- 1993/01/01 00:00
MHDA- 1993/01/01 00:01
CRDT- 1993/01/01 00:00
PHST- 1993/01/01 00:00 [pubmed]
PHST- 1993/01/01 00:01 [medline]
PHST- 1993/01/01 00:00 [entrez]
AID - 10.1111/j.1365-2184.1993.tb00005.x [doi]
PST - ppublish
SO  - Cell Prolif. 1993 Jan;26(1):45-54. doi: 10.1111/j.1365-2184.1993.tb00005.x.