The effect of vincristine on methotrexate uptake and inhibition of DNA synthesis by human lymphoblastoid cells.

Vincristine (VCR) has been shown to enhance the trans port of methotrexate (MTX) in animal systems and in acute myelogenous leukemia cells in vitro. In this report, the uptake of MTX and the effect of VCR were studied in two human lymphoblastoid cell lines grown in tissue culture. The effect of VCR on MTX suppression of deoxyuridine incorporation into DNA by these cell lines was also investi gated. The data indicate that an extracellular VCR concentration achievable following conventional single i.v. doses used clinically (0.1 /¿M) failed to enhance total intracellular MTX accumulation in either cell line at either conventional (1 ¿¿M) or "high-dose" (100 ¿¿M) extracellular MTX concentrations.