In vitro inhibition of murine hematopoietic progenitors and stromal cells by vinorelbine |
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Authors: | González-Cid M Larripa I de Di Risio CB |
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Institution: | (1) Departamento de Genética, Instituto de Investigaciones Hematológicas "Mariano R. Castex", Academia Nacional de Medicina, Buenos Aires, Argentina |
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Abstract: | 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 μg/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 appearence 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 μg/ml; and a marked loss at the dose of 0.1 μg/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 μg/ml), suggesting that the stroma is more resistant to this drug.
This revised version was published online in July 2006 with corrections to the Cover Date. |
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Keywords: | cytotoxicity hematopoietic progenitors murine bone marrow stromal cell layers vinorelbine |
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