Hydrogen peroxide and cytolytic factor can interact synergistically in effecting cytolysis of neoplastic targets

Two secretory products from activated macrophages, which are thought to be involved in the lysis of tumor cells, are H2O2 and cytolytic factor (CF). To examine the potential of interaction between these 2 mediators of cytolysis, we first exposed MCA-I sarcoma targets to the 2 lytic agents. MCA-I targets, which have been previously shown to be lysed by CF, could also be lysed by H2O2 (the concentration of H2O2 causing 50% lysis of targets was approximately 1.4 x 10(-3) M). Exposure of the MCA-I targets to a nonlytic concentration of H2O2 for 1 hr potentiated the subsequent lytic effects of CF and did so synergistically. Exposure of targets to CF, however, did not potentiate the subsequent lytic effects of H2O2, even when the targets were treated with a lytic concentration of CF for 4 hr. Similar results were seen with P-388 lymphoma targets. The P388 cells were quite sensitive to the lytic effects of H2O2 (the concentration of H2O2 causing 50% lysis of these targets was approximately 2.0 x 10(-5) M) but proved relatively resistant to CF in comparison to the MCA-I targets. The data suggest that H2O2 and CF can interact synergistically to produce cytolysis of neoplastic targets if the targets are exposed to the 2 substances in a defined sequence.