Effect of lithium on the myelosuppressive and chemotherapeutic activities of vinblastine.

Serum concentrations of lithium after i.p. administration to normal mice declined with biphasic kinetics. Treatment of mice bearing ascitic L1210 leukemia with lithium resulted in a modest protection against the myelosuppressive effects of vinblastine. Lithium as a single agent was without effect on the survival times of mice bearing either the L1210 or P388 leukemia. Similarly, there was no evidence of significant antiproliferative or cytotoxic activity when cultured L1210 leukemia and murine neuroblastoma cells were exposed to lithium at levels comparable to those observed in the serum of lithium-treated mice. The therapeutic activity of vinblastine against the L1210 and P388 leukemias was not significantly altered by either simultaneous or subsequent administration of lithium. Lithium did not antagonize the antiproliferative or cytotoxic action of vinblastine against L1210 leukemia or murine neuroblastoma cells and was without effect in experiments with neuroblastoma cells that assessed vinblastine inhibition of a biological function dependent on formation of cytoplasmic microtubules (neurite formation induced by serum deprivation). The results obtained suggest that administration of lithium to reduce myelosuppression is not likely to counteract the tumoricidal activity of vinblastine.