Flow Microfluorometric Analysis of P388 Murine Leukemia After Administration of Vincristine and Maytansine in Vivo

Maytansine is a new drug undergoing clinical investigation. It has functional similarities to vincristine. Maytansine and vincristine were given to CDF1 mice with P388 leukemic ascites, and the cytokinetic response of the tumor cells was analyzed with a flow microfluorometer; mithramycin was used as the DNA fluorochrome. The results indicated a similar series of cytokinetic effects after administration of both drugs, though these effects were greater and more persistent after maytansine was given. Although both drugs produced some degree of multinucleation and endoreduplication, vincristine produced a discrete population of cells with a DNA content (fluorescence) equivalent to octoploidy (8C). Microscopy of the sorted 8C cells at 24 hours indicated 54% multinucleation and 33% mitotic figures. Most cells remained blocked in the G1-phase for at least 96 hours after administration of both drugs, which indicated that rapid DNA content distributions can be used to determine not only the effects of drugs on cell cycle distribution but also the duration of drug action.