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.

Journal of Biological Response Modifiers
|October 1, 1989
PubMed

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.

Related Concept Videos

NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
Phagocytosis of Apoptotic Cells01:17

Phagocytosis of Apoptotic Cells

Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or  immature dendritic cells. Non-professional phagocytes such as  epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes. 
Normal cells contain receptors that prevent them from being recognized by phagocytes.
Necrosis01:16

Necrosis

Necrosis is considered as an “accidental” or unexpected form of cell death that ends in cell lysis. The first noticeable mention of “necrosis” was in 1859 when Rudolf Virchow used this term to describe advanced tissue breakdown in his compilation titled “Cell Pathology”.
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become anucleated and die, but their...
Cellular Injury IV: Necrosis01:16

Cellular Injury IV: Necrosis

Necrosis is a form of irreversible cell death caused by severe injury such as ischemia, toxins, or trauma. Unlike programmed cell death, it is an uncontrolled, pathological process that typically provokes inflammation in surrounding tissues.Pathophysiologic ChangesNecrosis begins when cells sustain critical damage, leading to swelling of organelles, particularly mitochondria, and rapid ATP depletion. As energy levels decline, membrane ion pumps fail, leading to calcium influx and eventually,...