DNA fragmentation and cytotoxicity caused by tumor necrosis factor is enhanced by interferon-gamma

Eur J Immunol. 1987 May;17(5):689-93. doi: 10.1002/eji.1830170517.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • DNA Damage*
  • Drug Synergism
  • Glycoproteins / toxicity*
  • Humans
  • Interferon-gamma / toxicity*
  • Sulfates / pharmacology
  • Tumor Necrosis Factor-alpha
  • Zinc / pharmacology
  • Zinc Sulfate

Substances

  • Glycoproteins
  • Sulfates
  • Tumor Necrosis Factor-alpha
  • Zinc Sulfate
  • Interferon-gamma
  • Zinc