In vitro inhibition of murine hematopoietic progenitors and stromal cells by vinorelbine.
Hematopoietic progenitor colony assays were used to establish the effects of the vinca alkaloid vinorelbine (VRB) on murine bone marrow. The in vitro growth of colony-forming units-granulocyte/macrophage (CFU-GM), burst forming units-erythroid (BFU-E) and colony-forming units-mix (CFU-mix) was dose-dependently inhibited by VRB. The highest dose assayed (0.02 microg/ml) suppressed all of the different progenitor cells by 100%. A comparison of the dose-response curves showed that CFU-GM, BFU-E, and CFU-mix exhibited similar-patterns of sensitivity to the cytotoxic action of VRB. Long-term bone marrow cultures have provided a valuable in vitro model for studying the role of the microenvironment of bone marrow. Cellularity of stromal layers was reduced with increasing doses of VRB. The appearance of these layers was altered minimally with the lowest dose used; a gradual loss of cellularity was seen in cultures exposed to 0.05 and 0.075 microg/ml; and a marked loss at the dose of 0.1 microg/ml. Our results show that VRB has an important effect on hematopoietic progenitors at the highest dose tested, while the stromal cells were not affected at a similar dose (0.025 microg/ml), suggesting that the stroma is more resistant to this drug.
González-Cid
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Departamento de Genética, Instituto de Investigaciones Hematológicas Mariano R. Castex, Academia Nacional de Medicina, Buenos Aires, Argentina. lacuteci@intramed.net.ar
Larripa
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de Di Risio
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CB
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000633:toxicity*; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D015672:Erythroid Precursor Cells / Q000166:cytology / Q000187:drug effects; D006098:Granulocytes / Q000166:cytology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects*; D008264:Macrophages / Q000166:cytology; D051379:Mice; D008807:Mice, Inbred BALB C; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects*; D014747:Vinblastine / Q000031:analogs & derivatives* / Q000633:toxicity; D000077235:Vinorelbine
D000972:Antineoplastic Agents, Phytogenic; D014747:Vinblastine; D000077235:Vinorelbine