Transport of the folate compound methotrexate decreases during differentiation of murine erythroleukemia cells.

Abstract The relationship of folate transport and chemically induced differentiation of murine erythroleukemia cells (MELC) was examined. MELC were found to have a carrier-mediated transport system for reduced folates. Chemically induced differentiation of MELC caused a 10-fold decrease in the rate of influx of the folate analog methotrexate. The loss of methotrexate transport during differentiation resulted from a 15-fold decrease in the Vmax for the influx while the Km remained unchanged. Inducer dose dependencies for hemoglobin accumulation and loss of methotrexate influx were similar. A dimethyl sulfoxide-resistant variant of MELC did not express complete accumulation of hemoglobin or loss of methotrexate transport when treated with dimethyl sulfoxide. The decrease of folate influx during differentiation was not a result of: 1) changes in cell densities or growth phase; 2) growth-related changes of the medium; or 3) a direct inhibition of folate influx by the inducers. Loss of folate compound transport correlated with MELC differentiation.