Alterations in the Kinetics of Methotrexate Transport During Growth of L1210 Murine Leukemia Cells in Culture

Measurements of methotrexate transport during different phases of growth of L1210 murine leukemia cells in culture revealed no significant change in the K m for methotrexate influx (3.9-4.7 µM) during growth. However, the V max for influx into exponentially growing (midlog) L1210 cells was threefold greater (9.4 nmol/min/g dry wt) than the V max for influx into stationary cells (3.1 nmol/min/g dry wt), while the rate of methotrexate efflux from stationary phase cells ( K , 0.06 min -1 ) was twice that measured for midlog cells ( K , 0.03 min -1 ). These reciprocal changes in the kinetic parameters for influx and efflux accounted for a five- to sixfold greater steady-state level for exchangeable methotrexate in midlog cells than in stationary phase cells. These data may help to explain the increased sensitivity of exponentially growing versus stationary phase cells to methotrexate.