Kinetics of methotrexate uptake by human tumor cells from routine pathological samples

The kinetics of cell uptake of methotrexate were measured in vitro using primary human tumor cells from malignant pleural effusions, leukemic cells from leukopheresis samples, and normal tonsillar lymphocytes. The results were consistent with either passive diffusion or carrier mediated uptake kinetics, with the latter applicable only under conditions where the extracellular concentration of methotrexate was smaller than the drug-transport receptor binding constant. The intial rates of uptake for the same cell type differed signicantly between patients; however no differences in uptake rates were noted between cell types. All three sources of cells proved suitable for uptake studies. The results suggest that the variation in response in normally methotrexate responsive neoplasms, such as leukemia or lymphoma, may be due to between-patient differences in the cellular rates of methotrexate uptake.