Effect of chemotherapeutic agents on natural and BCG-stimulated macrophage cytotoxicity in mice

Abstract

Spontaneous or Bacillus Calmette Guérin (BCG)-stimulated macrophage cytotoxicity was investigated in the peritoneal cavity of BALB/c × DBA/2 mice treated with various chemotherapeutic agents. The SV40-transformed mKSA TU5 (TU5) line and the mFS6 sarcoma were used as targets. Cytolytic activity of macrophages from individual mice (4–6 per experimental group) was measured as release of [ 3H methyl] thymidine from prelabelled target cells. Treatment with azathioprine (a single injection of 100–400 mg/kg or 5 daily doses of 10–80 mg/kg s.c.) and dimethyltriazenoimidazole carboxamide (a single injection of 45–180 mg/kg or 5 daily doses of 3–30 mg/kg i.v.) resulted in marked dose-dependent inhibition of spontaneous macrophage cytotoxicity against TU5 tumor cells 2 days later. By 7 days after drug treatment spontaneous cytotoxicity of macrophages had returned to normal levels. In contrast adriamycin (a single dose of 5–10 mg/kg or 5 daily doses of 0.6–2.5 mg/kg i.v.) and cyclophosphamide (a single dose of 50–200 mg/kg or 5 daily doses of 6–25 mg/kg i.v.) did not affect spontaneous cytolytic activity of murine macrophages. BCG-stimulated macrophage cytotoxicity was investigated using mFS6 target cells which were relatively resistant to the spontaneous levels of macrophage-mediated cytolysis; the same pattern of effects was observed, azathioprine and dimethyltriazenoimidazole carboxamide inhibiting cytolytic activity levels in contrast to adriamycin and cyclophosphamide. These results are discussed in terms of the known effects of these agents on other functions of mononuclear phagocytes and on other immune reactivities.