DNA fragmentation and cytotoxicity caused by tumor necrosis factor is enhanced by interferon‐γ

Recombinant human tumor necrosis factor (rhuTNF) induced DNA fragmentation in sensitive cell lines. This fragmentation was similar to that caused by lymphotoxincontaining 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 μM ZnSO4 inhibited the rhuTNF‐induced DNA cleavage in MCF‐7 cells. Recombinant interferon‐γ (rhuIFN‐γ) 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‐γ for 1 h prior to rhuTNF treatment also enhanced DNA fragmentation and cell killing.