DNA Fragmentation in Tumor Cells Mediated by Human Natural Killer Cells and Lymphokine-Activated Killer Cells

The authors quantitatively determined target-cell lysis (using a super(51)Cr-release assay) and target cell-DNA fragmentation (using radiolabeled DNA assays and agarose gel electrophoresis). The authors found that although NK lyse their sensitive targets at high effector-target (E/T) ratios, they also effectively fragment the target-cell DNA at low E/T ratios. This DNA damage of NK-sensitive human-tumor lines, such as K562 leukemia cells, can be mediated by fresh human NK, cloned NK lines, and IL-2-activated mononuclear cells. The DNA fragments induced in the human K562 leukemic cells are heterogeneous in size, ranging from 500-23,000 base pairs in length. The same effector cells induce multiples of 200 base pair fragments in mouse YAC-1 tumor-target cells, suggesting that the extent of DNA damage is target cell-dependent.