A differential interaction of daunomycin, adriamycin, and N-trifluoroacetyladriamycin 14-valerate with mouse peritoneal macrophages

Abstract

The interaction of three anthracycline drugs, daunomycin, Adriamycin, and N-trifluoroacetyladriamycin 14-valerate, with mouse peritoneal macrophages was explored. As assessed by drug-specific cytofluorescence, Adriamycin and daunomycin accumulated slowly within macrophages, first staining the nucleus and then the cytoplasmic inclusions that were induced by the drug treatment. N-Trifluoroacetyladriamycin 14-valerate distributed rapidly into the cells, was excluded from the nucleus, and induced numerous cytoplasmic inclusions. Electron microscopy revealed that the cytoplasmic inclusions were vacuoles containing some amorphous material and not the classical autophagic vacuoles containing organelles and membrane lamellae. All the drugs induced cell shrinkage with time and brought about cell death within 24 hr. Loss of cell function and viability was dose and time dependent; i.e., a 6-hr incubation with daunomycin or Adriamycin, 2.5 microgram/ml, brought about a 50% reduction in the phagocytic capacity of the treated macrophages. The damaging potency towards macrophages (daunomycin greater than Adriamycin greater than N-trifluoroacetyladriamycin 14-valerate) is in the reverse order to the in vivo therapeutic efficiency.