RT Journal Article
SR Electronic
T1 Alterations in the Kinetics of Methotrexate Transport During Growth of L1210 Murine Leukemia Cells in Culture
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 274
OP 280
VO 18
IS 2
A1 PAUL L. CHELLO
A1 FRANCIS M. SIROTNAK
A1 DIANE M. DORICK
YR 1980
UL http://molpharm.aspetjournals.org/content/18/2/274.abstract
AB Measurements of methotrexate transport during different phases of growth of L1210 murine leukemia cells in culture revealed no significant change in the Km for methotrexate influx (3.9-4.7 µM) during growth. However, the Vmax for influx into exponentially growing (midlog) L1210 cells was threefold greater (9.4 nmol/min/g dry wt) than the Vmax 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. ACKNOWLEDGMENT The authors wish to thank Ms. Ellen Wong for excellent technical assistance.