Document Detail


Cytotoxicity by tumor necrosis factor is linked with the cell cycle but does not require DNA synthesis.
MedLine Citation:
PMID:  2634429     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The relationship between the kinetics of cell death induced by TNF and the cell cycle in L929.10 target cells was investigated by comparison of growing, asynchronous cells with target cells synchronized at G1/S using a double thymidine block. The induction phase of lysis, the time following TNF addition but before loss of cell viability, was shortened in asynchronous cells by increasing the level of saturation of the TNF receptor. However, in synchronized target cells, the length of the induction phase showed no dependence on receptor occupancy. Almost all cell death occurred within a 3 hr period 4-7 hr after the addition of TNF regardless of the concentration of TNF. Target cell lysis in synchronized cells was concomitant with mitosis as verified by flow cytometry and DNA staining with propidium iodide. The narrow window of cytotoxicity was not due to cell cycle-related changes in the expression of the TNF receptor as measured by [125I]TNF binding. Treatment with TNF did not accelerate or retard the progression of cells through S and G2/M nor did target cells accumulate at G2/M. When the kinetic experiments were repeated in the presence of 2 mM thymidine, TNF-treated cells died with identical dose and kinetic responses as those in which the thymidine block had been removed. Under these conditions, flow cytometric analysis revealed that DNA synthesis remained inhibited. These results suggest that TNF-induced cytotoxicity is linked to cell cycle-associated processes and that TNF is capable of overriding the normal cellular controls that coordinately link the DNA replicative cycle with the mitotic cycle. In the L929.10 target cell, TNF may induce a fatal mitosis-linked event.
Authors:
F D Coffman; D L Haviland; L M Green; C F Ware
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Growth factors (Chur, Switzerland)     Volume:  1     ISSN:  0897-7194     ISO Abbreviation:  Growth Factors     Publication Date:  1989  
Date Detail:
Created Date:  1990-06-06     Completed Date:  1990-06-06     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9000468     Medline TA:  Growth Factors     Country:  SWITZERLAND    
Other Details:
Languages:  eng     Pagination:  357-64     Citation Subset:  IM    
Affiliation:
Division of Biomedical Sciences, University of California, Riverside 92521.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Cycle*
Cell Division / drug effects
Cell Line
Cytotoxicity, Immunologic / drug effects
DNA / biosynthesis*
Flow Cytometry
Mice
Tumor Necrosis Factor-alpha / pharmacology*
Grant Support
ID/Acronym/Agency:
AM 07310/AM/NIADDK NIH HHS; CA35638/CA/NCI NIH HHS; RR 05816/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Tumor Necrosis Factor-alpha; 9007-49-2/DNA

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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