[Induction of activated macrophages by intraperitoneal injection of mitomycin C in mice and rats]

The local cellular response induced by i.p. injection of mitomycin C (MMC) was studied in C3H/HeN mice and ACI/N rats. MMC-induced peritoneal macrophages showed the maximum in vitro tumoricidal activity against 125I-UdR-labeled syngeneic tumor target cells 4 to 7 days after the i.p. injection of MMC at a single dose of 3 mg/kg and 1 mg/kg in mice and rats, respectively. The tumoricidal activity was dependent on the dose of mitomycin C injected and it was alos detectable against allogeneic and xenogeneic tumor target cells. In addition, these tumoricidal macrophages were found to have augmented functions of 2-deoxy-D-glucose incorporation and phagocytosis. Additional experiments excluded the possibility that the tumor cell cytolysis was the result of direct cytotoxicity of MMC that might have been incorporated into the peritoneal macrophages or of nutrient depletion in the medium during the cytolysis assay. Although the mechanism by which MMC injected i.p. induced the tumoricidal macrophages locally remained undetermined, in vitro production of macrophage-activating factor (MAF) from splenocytes cultured with concanavalin A was enhanced remarkably, following exposure of the spleen to MMC in vivo or in vitro, indicating the involvement of lymphokine in the induction of tumoricidal macrophages by MMC. Among other anticancer drugs, which were used at a dose of three-fifths of LD50, only adriamycin (7.5 mg/kg) was capable of inducing tumoricidal macrophages. A better understanding of the effect of anticancer drugs on macrophage tumoricidal activity may be useful in designing more effective local chemotherapy for cancerous peritoneal effusions.