TUMORICIDAL EFFECT OF MACROPHAGES EXPOSED TO ADRIAMYCIN INVIVO OR INVITRO

Abstract

Peritoneal macrophages from BD IX rats collected 24 h after an i.p. injection of adriamycin [Adr] (10 mg/kg) were cytotoxic to syngeneic cancer cells in culture. In contrast, incubation in vitro in Adr solutions did not evoke tumoricidal activity in peritoneal macrophages, whatever the incubation time (from 1-24 h) and the Adr concentration (from 1 ng to 100 .mu.g/ml). Macrophages incubated with Adr, in vitro accumulated the drug in their nuclei, whereas macrophages from animals receiving Adr in vivo accumulated it in cytoplasmic vacuoles. Early observation of peritoneal cells after in vivo exposure to Adr shows that Adr is concentrated in mast cell granules which are released and then phagocytosed by peritoneal macrophages. Mast cells exposed to Adr in vitro can induce macrophages to become cytotoxic. These facts explain the difference between macrophages exposed to Adr in vivo and in vitro. Adr fluorescence appears in nuclei of cancer [rat colon carcinoma DHD-K12 cells] cells incubated with in vivo-labeled macrophages, suggesting that macrophages can directly transfer the drug into cancer cells and therefore play a role in the Adr antitumor effect.