Tumor necrosis factor induced DNA fragmentation of HL-60 cells

Tumor necrosis factor (TNF) induces differentiation of HL-60 cells, with only slight effects upon proliferation and little or no cytotoxicity. TNF induced cytotoxicity of other target cell lines has been associated with DNA fragmentation. To assess whether TNF-induced DNA fragmentation might also contribute to HL-60 differentiation, studies were performed using a 3H]-dThd release assay. Between 1 and 2 hours of culture, significant 3H]-dThd release was induced by TNF at concentrations of 10 U/ml and greater. This response was blocked by inhibiting energy metabolism, but not by several inhibitors of cell surface signal transduction, protein or RNA synthesis, or free radical scavengers. DNA electrophoresis of the released DNA disclosed a wide range of low molecular weight fragments. It is possible that TNF-induced DNA fragmentation contributes to HL-60 differentiation.