MULTIPLE TUMORICIDAL EFFECTOR MECHANISMS INDUCED BY ADRIAMYCIN

  • 1 January 1984
    • journal article
    • research article
    • Vol. 44  (6) , 2561-2566
Abstract
The antitumor cytotoxic mechanisms of adriamycin-elicited peritoneal exudate cells were investigated. Peritoneal exudate cells from mice collected 1 day after an i.p. injection of adriamycin 10 mg/kg) displayed enhanced cytotoxicity against P815 [mouse mastocytoma] (natural killer-insensitive, macrophage-sensitive) but not YAC-1 [mouse lymphoma] (natural killer-sensitive) tumor cell lines. These cells contained a sufficient concentration of the drug to be cytotoxic for P815 tumor cells in 18-h Cr release assays. Freeze-thaw lysates of these peritoneal exudate cells were as cytotoxic to P815 as their corresponding whole cells. The lytic activity of these lysates was removed by centrifugation at 100,000 .times. g, indicating the insolubility of the effector moiety. These cells produced significant amounts of superoxide anion and H2O2 in response to phorbol myristate acetate. A catalase-inhibitable augmentation of the cytotoxicity of these cells against P815 was observed when phorbol myristate acetate was added to the assay. Neutrophils and not macrophages were likely responsible for this effect. Peritoneal lymphocytes from mice given injections of adriamycin 5-7 days previously were cytotoxic to YAC-1 tumor cells in 4-h assays. Peritoneal macrophages harvested 5-7 days after adriamycin administration were cytotoxic to P815 in the absence of detectable Adriamycin. The addition of phorbol myristate acetate inhibited by the lysis of P815 by these cells.