Cell cycle-dependent tumor necrosis factor apoptosis Journal Article


Authors: Shih, S. C.; Stutman, O.
Article Title: Cell cycle-dependent tumor necrosis factor apoptosis
Abstract: To determine if tumor necrosis factor (TNF)-mediated apoptosis affects cells at defined stages of the cell cycle, WEHI-164/2F (WEHI) cells were synchronized at G0-G1 after 3-day cultures in medium containing RPMI 1640 and 0.5% FCS (RPMI-0.5% FCS). The arrested WEHI cells (60-75% in G0-G1) showed increased sensitivity to TNF killing, measured as 48-h 3-(5- dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assays, and 15-h apoptosis by propidium iodide staining and flow cytometry analysis. The TNF killing kinetics of G0-G1-arrested cells was similar to controls, and TNF did not accelerate or retard cell cycle progression of the arrested cells after feeding with fresh RPMI-0.5% FCS. However, TNF inhibited WEHI DNA synthesis as early as 1 h after treatment, and inhibition was proportionate to sensitivity to TNF-induced apoptosis. WEHI cells treated with TNF showed a higher percentage of cells in S phase with concomitant decrease in G0-G1 and G2-M. When cultured for 3-18 h in fresh RPMI-0.5% FCS to allow progression of the G0-G1-arrested cells toward the G1-S boundary, WEHI cells became more sensitive to TNF killing, especially at the 3-9-h time points. Moreover, TNF did not degrade [125I]5-iodo-2'-deoxyuridine- labeled WEHI DNA if the labeled cells were precultured for 9 h in fresh RPMI- 0.5% FCS to allow them to pass S phase before the addition of TNF. These results show that TNF-induced apoptosis of WEHI cells is connected to cell cycle events; WEHI targets receive the TNF cytotoxic signal mainly at the G1-S boundary and begin to die by apoptosis as they exit from S phase.
Keywords: controlled study; dose response; nonhuman; solid tumor; dna replication; dna synthesis; animal cell; mouse; dna damage; cell cycle; apoptosis; cytotoxicity; tumor cells, cultured; cytokine; tumor necrosis factor-alpha; recombinant tumor necrosis factor; g1 phase; s phase; tumor necrosis factor; g0 phase; humans; priority journal; article
Journal Title: Cancer Research
Volume: 56
Issue: 7
ISSN: 0008-5472
Publisher: American Association for Cancer Research  
Date Published: 1996-04-01
Start Page: 1591
End Page: 1598
Language: English
PUBMED: 8603407
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 22 November 2017 -- Source: Scopus
Citation Impact
MSK Authors
  1. Osias   Stutman
    45 Stutman