Study of the action of tumor necrosis factor
Tumor necrosis factor (TNF) is a cytokine produced by macrophages that mediates a host of biological effects. These effects include a modulation of cell growth, an antitumoral effect, an antiviral effect, an effect on the host's immune system, an effect on endothelial cells, and various effects on gene transcription. Incubation conditions such as an elevated temperature, the presence of metabolic inhibitors, and amino acid deprivation, enhance the anticellular effect of TNF. The in vivo administration of the combination of TNF and glutaminase, an enzyme that reduces the circulating levels of glutamine, enhances the survival times of mice bearing the Meth A sarcoma. A similar enhancement of TNF's antitumoral efficacy has been observed in tumor-bearing animals that received the combined therapy of TNF and azaleucine, an amino acid that gets incorporated into cellular proteins resulting in the production of non-functional proteins, and results in complete cures of some of the tumor-bearing mice. TNF treatment of cells sensitive to the anticellular action of TNF causes the fragmentation of their cellular DNA into multiples of approximately 200 base pairs. TNF fails to mediate this effect in cells resistant to the anticellular action of TNF. Factors affecting the rate at which TNF mediates its anticellular effect have a similar effect on the rate of DNA fragmentation. These results thus reveal a correlation between these two TNF-mediated effects and suggest that the monitoring of the effect of TNF on the DNA of tumor tissues may allow for the selection of those individuals whose tumors are likely to respond to the anticellular action of TNF. ^
Smith, Larry Joe, "Study of the action of tumor necrosis factor" (1989). ETD Collection for Fordham University. AAI8918644.