Inhibition of murine CFU-C by vindesine: restoration of colony growth by colony stimulating factor.
Vindesine (VDS) is a new vinca-alkaloid related to vinblastine and vincristine that blocks production of the microtubules in the mitotic phase of the cell cycle. Studies were undertaken to investigate the inhibitory effect of VDS on normal murine bone marrow cell proliferation and the possible interactions between this compound and L-cell derived colony stimulating factor (CSF). One X 10(7) murine bone marrow cells were exposed to various concentrations of VDS, ranging from 0.1 to 1.5 micrograms/ml for 1 h at 37 degrees C. Following this period, the cells were plated in agar in the presence of 100 units of CSF. A dose-dependent inhibition of colony formation was noted with increasing doses of the drugs. To determine whether an increased dose of CSF could overcome the inhibitory effect of VDS, further studies compared colony growth in response to 100 and 200 units of CSF. Virtually no inhibition of colony growth was detected in VDS-treated cells exposed to this higher dose of CSF while a dose-dependent reduction in CFU-C was noted with 100 units of CSF. Preincubation of cells with VDS and CSF prevented the inhibition that occurred with VDS alone. The addition of anti-CSF serum during the preincubation phase abolished the protective effect of CSF. The studies show that short-term exposure of marrow cells to VDS causes a dose-dependent inhibition of in vitro colony formation; this inhibition is prevented by increasing doses of CSF in agar culture or by simultaneous preincubation with CSF. The CSF action appears specific as its protective effect is neutralized by antibody to CSF, suggesting a potential role for CSF in preventing the antimitotic activity of VDS.
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006410:Hematopoiesis / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D007106:Immune Sera; D066298:In Vitro Techniques; D051379:Mice; D014747:Vinblastine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014751:Vindesine
D003115:Colony-Stimulating Factors; D007106:Immune Sera; D014747:Vinblastine; D014751:Vindesine