DNA fragmentation and cytotoxicity caused by tumor necrosis factor is enhanced by interferon-gamma.
Recombinant human tumor necrosis factor (rhuTNF) induced DNA fragmentation in sensitive cell lines. This fragmentation was similar to that caused by lymphotoxin-containing cytotoxic T cell culture supernatants. The percentage of DNA cleaved correlated with the degree of cell growth inhibition shown by individual cell lines. DNA fragmentation was first seen after 12 h treatment, and increased slowly with time. The presence of 100 microM ZnSO4 inhibited the rhuTNF-induced DNA cleavage in MCF-7 cells. Recombinant interferon-gamma (rhuIFN-gamma) did not induce DNA cleavage, although it reduced the growth of all the cell lines used in this study. However, it interacted with rhuTNF to produce a doubling in the percentage of DNA fragmentation, and increased cytotoxicity in rhuTNF-sensitive cell lines. Pretreatment with rhuIFN-gamma for 1 h prior to rhuTNF treatment also enhanced DNA fragmentation and cell killing.
D002478:Cells, Cultured; D004249:DNA Damage; D004357:Drug Synergism; D006023:Glycoproteins / Q000633:toxicity*; D006801:Humans; D007371:Interferon-gamma / Q000633:toxicity*; D013431:Sulfates / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha; D015032:Zinc / Q000494:pharmacology; D019287:Zinc Sulfate
D006023:Glycoproteins; D013431:Sulfates; D014409:Tumor Necrosis Factor-alpha; D019287:Zinc Sulfate; D007371:Interferon-gamma; D015032:Zinc