Significance of Intracellular TNF as a Resistant Factor against the Cytotoxicity of TNF : Proof by DNA Transfection Method

Based on previous findings that intracellular tumor necrosis factor (TNF) which is not detectable in TNF-sensitive cells was expressed in TNF-resistant cells, the assumption was made that intracellular TNF may be a resistant factor against the cytotoxic activity of TNF. In order to confirm this possibility, we investigated the relationship between the expression of intracellular TNF and TNF susceptibility by the DNA transfection method. When L-M, highly TNF-sensitive murine fibrosarcoma cells, were transfected with a human TNF gene, the stable transfectants expressed intracellular TNF and acquired resistance to TNF. Conversely, when TNF synthesis was inhibited by introducing an antisense TNF gene into HeLa, less TNF-sensitive human cervical cancer cells, the sensitivity was enhanced. These findings indicate that intracellular TNF is one of the resistant factors against the cytotoxic activity of TNF