In vitro sensitivity of normal granulocytic and lymphoma colonies to vinca alkaloids

Recently, a colony-forming assay was developed in our laboratory for pediatric malignant lymphoid diseases. This assay supports the growth of lymphoma colonies (ML-CFC) as well as normal granulocytic colonies (CFU-C) and thus a direct comparison between the antineoplastic and myelosuppressive effects of a drug can be determined. To test specificity of this in vitro assay to structurally similar drugs, the inhibitory effects of three vinca alkaloids (vincristine, vindesine, vinblastine) on ML-CFC (B-, T-, pre-T-cell types) and CFU-C was determined. Our results demonstrate that all three vinca alkaloids were active agents in vitro and that a direct dose response effect occurred once a threshold dose was reached. Each vinca alkaloid had a different pattern of inhibitory effect on ML-CFC and CFU-C suggesting an inherent difference in drug metabolism by these cells. Also, based on the dose inhibiting 50% of colony formation, vinblastine was 94 times more inhibitory against malignant B-cell ML-CFCs than against granulocytic CFU-C.