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.
Cancer 51:417-422, 1983.
ECENTLY, colony forming cell assays have been R developed for solid tumors"' and acute leuke-mias3q4 In these assays, single malignant cells divide six or more times and produce a colony of greater than 50 cells in seven to 18 days. Studies on the in vitro growth of colony forming cells have defined factors responsible for growth and differentiation of both normal and malignant cells.5*6 In addition in vitro drug sensitivity patterns on the colony forming cells have been predictive of the individual patient's response to chem~therapy.'.~ To test drug specificity of this in vitro assay, the effect of the vinca alkaloids on the colony forming ability of both normal granulocytic and malignant lymphoid cells was evaluated. The three vinca alkaloids in current clinical use are vincristine, vinblastine, and vindesine. De-From the