Cytotoxic thresholds of vincristine in a murine and a human leukemia cell line in vitro.

L1210 murine leukemia and CEM human lymphoblastoid leukemia cells were exposed to vincristine sulfate in vitro. The response of these cell lines to this agent was measured by the colony-forming ability of L1210 cells in soft agar and inhibition of growth of CEM in suspension culture. Incremental increases of vincristine concentrations in excess of 2 x 10(-9) M produced a progressive reduction of survival of L1210 cells and suppression of CEM growth under the condition of constant drug exposure. A maximum cytotoxic effect was reached with drug concentrations between 10(-8) and 10(-7) M. When L1210 cells were exposed to vincristine for a variable length of time ranging from 0.5 to 24 hr, 10(-7) M produced a noticeable cytotoxic effect following an incubation of only 30 min. A 50% cell kill of L1210 cells and a 50% reduction of CEM cell growth were produced by 10(-7) M following a 1- to 3-hr period of exposure; 6 to 12 hr were required to produce a similar effect at a vincristine concentration of 10(-8) M. Therefore, the antitumor effect of vincristine is critically dependent on both concentration and duration of exposure. These data suggest the possibility that the effectiveness of vincristine as an antitumor agent could be enhanced if methods are developed to prolong exposure of neoplastic tissues for longer periods of time than currently produced by conventional methods of administration.