The synergistic tumoricidal activity of anticancer drugs and oxidative burst-triggered macrophages.
The anticancer drugs adriamycin (ADR) and actinomycin D (AMD) were tested for their effect on the oxidative burst (OB) of mouse peritoneal macrophages (MPM) and on the killing of tumor cells by OB-stimulated MPM. The oxidative burst of MPM determined by hydrogen peroxide (H2O2) production was severely impaired by ADR (10 micrograms/ml) and AMD (40 micrograms/ml) after a 1 h treatment and by lower concentrations of the drugs following a 24 h treatment. The toxicity of the drugs against MPM was comparable to their effect on EL4 cells. Pretreatment of EL4 and TLX-9 tumor cells with sublethal amounts of ADR for 4 h rendered the cells sensitive to the cytotoxic effect of OB-stimulated MPM which were otherwise unable to kill these cells. It seems that anticancer drugs and OB-stimulated macrophages can cooperate in the destruction of tumor cells in vitro.
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology / Q000627:therapeutic use*; D002470:Cell Survival / Q000187:drug effects; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D003609:Dactinomycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000378:metabolism; D007111:Immunity, Cellular; D008223:Lymphoma / Q000628:therapy*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D010101:Oxygen Consumption
D000903:Antibiotics, Antineoplastic; D003609:Dactinomycin; D004317:Doxorubicin; D006861:Hydrogen Peroxide; D005472:Fluorouracil