EFFECTS OF DOXORUBICIN ON THE CANINE ERYTHROID AND MYELOID PROGENITOR CELLS AND BONE-MARROW MICROENVIRONMENT

The antineoplastic drug doxorubicin is known to cause cytopenias. In humans and in dogs treated with doxorubicin, neutropenia is a common haematological toxicity. To determine the mechanism of doxorubicin haematotoxicity in the dog, in vitro bone marrow progenitor and microenvironment assays were done in the presence of doxorubicin. The 50% inhibitory concentration (IC50) of doxorubicin for canine erythroid colony-forming unit (CFU-E) was 0.042 +/- 0.01 muM and for canine granulocyte-macrophage colony-forming unit (CFU-GM) it was 0.0084 +/- 0.002 muM. To determine the effects of doxorubicin on the bone marrow microenvironment, fibroblast colony-forming unit (CFU-F) assays were performed. The 50% inhibitory concentration for canine CFU-F was 0.030 +/- 0.01 muM. Morphologically, the CFU-F were made up of predominantly cells (73 +/- 8%) with fibroblast-like morphology. Within the colonies as well as between the colonies, there were cells with macrophage (27 +/- 8%) morphology. To support the morphological classification of these cells, cytochemical staining was done. The cells with the fibroblast-like morphology were negative for butyrate esterase and those with macrophage morphology were positive, whereas both cell types were positive for acid phosphatase in the presence or absence of tartrate. Our data show that the effects of doxorubicin on in vitro haematopoiesis in the dog are similar to those described in man.