Observations on the intracellular accumulation of methotrexate and 5-methyltetrahydrofolate in uninduced, dimethylsulphoxide-induced and 1,25-dihydroxyvitamin D3-induced HL60 cells, and blood-monocyte-derived human macrophages.

The 90-min-uptake (37 degrees C) of 3H-methotrexate (3H-MTX) by uninduced HL60 cells was inhibited by 2,4-dinitrophenol, iodoacetate, ouabain, p-chloromercuriphenylsulphate and p-chloromercuribenzoate indicating its dependence on intracellular ATP, the Na+ and K+-activated ATPase of the cell membrane and sulphydryl groups on the cell surface. There was a marked reduction in the 90-min-uptake (37 degrees C) of 3H-MTX and 14C-methyltetrahydrofolate (14C-mTHF) when HL60 cells were induced to differentiate into neutrophil myelocytes and metamyelocytes by incubation with DMSO; a smaller reduction was seen when HL60 cells were induced to differentiate into mononuclear phagocytes by incubation with 1 alpha,25-dihydroxyvitamin D3 ([OH]2D3). Although it has been reported that the transport system mediating folate uptake has a higher Km value for mTHF and MTX in normal than in malignant cells, the Km values for these substrates were lower in blood-monocyte-derived macrophages than in uninduced HL60 cells or [OH]2D3-induced-macrophages. Values for the 90-min-uptake (37 degrees C) of 3H-MTX and 14C-mTHF in human blood-monocyte-derived macrophages were higher than the corresponding values in uninduced HL60 cells and [OH]2D3-induced macrophages.