In vivo methotrexate transport in murine Lewis lung tumor.
Methotrexate uptake by murine Lewis lung tumor was measured in vivo over a wide dose range. The data were analyzed according to a model previously developed for tissues in which methotrexate uptake is rate limited by transport across the cell membrane. Methotrexate transport in this tumor followed Michaelis-Menten kinetics with a rate constant for permeability (k/K) of 0.012 min-1. The methotrexate binding capacity of dihydrofolate reductase in the tumor was not exceeded at any dose studied. A low membrane permeability in conjunction with a high dihydrofolate reductase level explains the resistance of this tumor to methotrexate.
D000818:Animals; D001692:Biological Transport; D002463:Cell Membrane Permeability; D004305:Dose-Response Relationship, Drug; D008175:Lung Neoplasms / Q000378:metabolism*; D008297:Male; D008727:Methotrexate / Q000097:blood / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D009374:Neoplasms, Experimental / Q000378:metabolism; D013762:Tetrahydrofolate Dehydrogenase / Q000378:metabolism; D013997:Time Factors
D013762:Tetrahydrofolate Dehydrogenase; D008727:Methotrexate