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Correlation between the anticellular and DNA fragmenting activities of tumor necrosis factor
B Y Rubin1, L J Smith, G R Hellermann
1Department of Lymphokine Biology, New York Blood Center, New York 10021.
Abstract:
The treatment of cells sensitive to the anticellular effect of tumor necrosis factor (TNF) with TNF results in a degradation of their cellular DNA into DNA fragments that are multiples of 200 base pairs. TNF treatment of cells resistant to the anticellular effect of TNF, but bearing receptors for TNF, fails to result in any DNA fragmentation. Incubation conditions, such as temperature, the presence of metabolic inhibitors or amino acid deprivation, that modulate the effectiveness of TNF or affect the rate at which TNF exerts its anticellular effect have a similar effect on the ability of the TNF to generate DNA fragments. Thus the TNF-mediated DNA fragmentation and the rate at which it occurs correlates with the rate at which cells respond to the anticellular effect of TNF and, as such, might serve as a marker for the responsiveness of cells to TNF.
Insights
Tumor necrosis factor (TNF) treatment causes DNA fragmentation in sensitive cells, generating fragments in 200 base pair multiples. This DNA fragmentation correlates with cellular response to TNF, potentially serving as a responsiveness marker.
Area of Science:
- Cell biology
- Molecular biology
- Immunology
Background:
- Tumor necrosis factor (TNF) is a cytokine with significant biological effects.
- TNF mediates cellular responses, including cell death, in sensitive cells.
- The precise mechanisms and markers of TNF sensitivity are crucial for understanding its role.
Purpose of the Study:
- To investigate the relationship between TNF treatment and DNA fragmentation.
- To determine if DNA fragmentation can serve as a marker for cellular responsiveness to TNF.
- To explore factors influencing TNF-induced DNA fragmentation.
Main Methods:
- Treatment of sensitive and resistant cells with TNF.
- Analysis of DNA fragmentation patterns using gel electrophoresis.
- Modulation of incubation conditions (temperature, metabolic inhibitors, amino acid deprivation) to assess their impact on TNF effects.
Main Results:
- TNF treatment induced DNA fragmentation into multiples of 200 base pairs in sensitive cells.
- Cells resistant to TNF's anticellular effects, despite bearing TNF receptors, did not exhibit DNA fragmentation.
- Incubation conditions that modulated TNF's anticellular effectiveness also affected the rate and extent of DNA fragmentation.
Conclusions:
- TNF-mediated DNA fragmentation is a hallmark of TNF-sensitive cells.
- The rate of DNA fragmentation correlates with the cellular response to TNF.
- TNF-induced DNA fragmentation can potentially serve as a marker for predicting cellular responsiveness to TNF.