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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
Published on: December 27, 2016
Fragmentation of cellular DNA is a nonspecific indicator of responsiveness to tumor necrosis factor
B Y Rubin1, S L Anderson, R M Lunn
1Department of Lymphokine Biology, New York Blood Center, New York 10021.
Abstract:
Tumor necrosis factor (TNF) or lymphotoxin (LT) treatment of cells sensitive to the anticellular action of TNF results in the degradation of their cellular DNA into fragments that are multiples of about 200 base pairs. The specificity of this DNA fragmenting effect was examined. The DNA of cells dying either as a result of exposure to interferon-gamma (IFN-gamma) or as a result of having exhausted their culture media was observed to be fragmented into multiples of 200 base pairs. Antibody to TNF or LT failed to block the IFN-gamma-mediated DNA fragmentation and antibodies to IFN-gamma, TNF, and LT failed to block the DNA fragmentation observed in the cells dying as a result of having exhausted their culture media. Thus the fragmentation of cellular DNA appears to be nonspecific effect of cell death that can be induced by a variety of treatments.
Insights
Tumor necrosis factor (TNF) and lymphotoxin (LT) induce DNA fragmentation in sensitive cells. This DNA fragmentation is a nonspecific effect of cell death, observed across various treatments like interferon-gamma (IFN-gamma) and nutrient deprivation.
Area of Science:
- Molecular Biology
- Cell Biology
- Immunology
Background:
- Tumor necrosis factor (TNF) and lymphotoxin (LT) are cytokines known to induce programmed cell death.
- TNF-sensitive cells exhibit DNA degradation into fragments of approximately 200 base pairs upon treatment with TNF or LT.
- The specificity of this DNA fragmentation mechanism requires further investigation.
Purpose of the Study:
- To determine if the DNA fragmentation induced by TNF/LT is a specific effect or a general marker of cell death.
- To investigate the DNA fragmentation patterns in cells undergoing death induced by interferon-gamma (IFN-gamma) and nutrient deprivation.
Main Methods:
- Cells sensitive to TNF/LT were treated with TNF or LT, IFN-gamma, or cultured until media exhaustion.
- DNA fragmentation patterns were analyzed by gel electrophoresis.
- Antibodies against TNF, LT, and IFN-gamma were used to block specific cytokine effects.
Main Results:
- Treatment with TNF or LT resulted in DNA fragmentation into multiples of approximately 200 base pairs.
- Cells undergoing IFN-gamma-induced death or death due to media exhaustion also showed DNA fragmentation into multiples of 200 base pairs.
- Antibodies against TNF/LT did not inhibit IFN-gamma-induced DNA fragmentation, and antibodies against IFN-gamma, TNF, and LT did not inhibit DNA fragmentation in cells dying from media exhaustion.
Conclusions:
- The observed DNA fragmentation into multiples of 200 base pairs is not specific to TNF/LT treatment.
- This DNA fragmentation is a general characteristic of cellular demise, irrespective of the inducing agent.
- The study suggests that DNA fragmentation is a common, nonspecific endpoint of various cell death pathways.
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