Chonnam Med J.  1996 Dec;32(2):177-186.

The Study on cell death induced by tumor necrosis factor alpha

• Won YH
• Lim MH
• Kim DY
• Chun IK

Abstract

BACKGROUND: Tumor necrosis factor alpha(TNF) is a pleiotropic cytokine mainly produced by activated macrophages. Besides its role in the inflammation and immune function, TNF is specifically cytotoxic for many types of transformed cells. The cytotoxicity induced by TNF may occur through both types of cell death named necrosis and apoptosis. Being closely related to TNF-induced cytotoxicity, Reactive oxygen species is not unclear at its exact role on the mechanism of cell necrosis and apoptosis. OBJECTS: To see any difference according to cell types on the cell necrosis and apoptosis induced by TNF alpha, and the effect of several antioxidants and actinomycin D on TNF-induced cell death. MATERIALS AND METHOD: DNA fragmentation assay, in situ cell death by Tunnel method, trypan blue test and neutral red test were performed in L929 originated from mouse fibroblast and A431 from human squamous cell line treated by TNF and/or actinomycin D or antioxidants.
RESULTS
DNA fragmentation in A431 cells observed at the treatment of TNF 500 units/ml for 24 hours without any significant changes of cell viability. On the other hand, L929 cells revealed it at 250 units/ml for 12 hours, which increased at time dependent fashion except high doses of 1000 units/ml. Cell viability of L929 decreased in dose dependent fashion as 41% in 500 units for 24 hours. It was decreased significantly in TNF plus actinomycin D(1 g/ml) than those of TNF alone. DMSO (400mM) 'hydroxy radical scavenger' was significantly effective at preventing TNF induced cytotoxicity in 69%. The others including catalase, SOD, glutathion, ascorbic acid were also slightly effective. Their preventing effects were more decreased at TNF plus actinomycin D than those of TNF alone.
CONCLUSION
These results support that apoptosis and necrosis may occur differentially according to cell types and oxygen free radicals involve in TNF-induced cell death.

MeSH Terms

Animals
Antioxidants
Apoptosis
Ascorbic Acid
Catalase
Cell Death*
Cell Line
Cell Survival
Dactinomycin
Dimethyl Sulfoxide
DNA Fragmentation
Fibroblasts
Free Radicals
Hand
Humans
Inflammation
Macrophages
Mice
Necrosis
Neutral Red
Oxygen
Reactive Oxygen Species
Trypan Blue
Tumor Necrosis Factor-alpha*
Antioxidants
Ascorbic Acid
Catalase
Dactinomycin
Dimethyl Sulfoxide
Free Radicals
Neutral Red
Oxygen
Reactive Oxygen Species
Trypan Blue
Tumor Necrosis Factor-alpha