Influence of 12-O-tetradecanoylphorbol-13-acetate (TPA) on the susceptibility of K562 to natural cytotoxicity: evidence for clonal variation in differentiation-induced changes of lytic sensitivity.

The effect of 12-O-tetradecanoylphorbol-13-acetate (TPA) on the sensitivity to NK cell-mediated lysis of two cloned populations of K562 which exhibit marked and stable differences in their susceptibility to natural cytotoxicity has been examined. Culture in medium supplemented with TPA concentrations of l ng/ml or more invariably caused a decrease in the susceptibility of the sensitive clone E10/P2, whereas treatment of the relatively resistant clone F9/P2 with TPA under identical conditions caused a significant increase in susceptibility to natural cytotoxicity. In both cases the change in susceptibility occurred within 1 day of culture in TPA and was rapidly reversible following removal of the inducing agent. The changes in resistance to natural cytotoxicity induced by TPA were independent of variations in osmotic fragility and were not attributable to alterations in NK cell binding capacity as determined by cold competition analysis. In contrast to the effect of TPA, exposure of E10/P2 and F9/P2 to interferon (IFN) caused a reduction in sensitivity to natural cytotoxicity of both populations which was associated with a decreased capacity to compete for lysis of labelled target cells. These data suggest that the effects of differentiating agents on target susceptibility to NK cell lysis are variable and that responses to TPA are clonally distributed within cell populations.