Uptake of Tritiated Folates by Human Bone Marrow Cells in Vitro

Summary. Using incubation periods up to 4 hr, it was demonstrated that uptake of tritiated pteroylglutamic acid ([³H]PteGlu) by human bone marrow cells in vitro was in the range of six‐fold greater than uptake by reticulocytes. Uptake was temperature‐dependent, increasing during 4 hr at 37°C but not at 4°C; a similar temperature dependence was found for the uptake of [³H]methyltetrahydrofolate ([³H‐CH₃]H₄PteGlu). The pH optimum for [³H]PteGlu uptake was in the range of 7.4. Percentage uptake decreased as concentration of [³H]PteGlu increased. Preincubation with unlabelled PteGlu reduced uptake of subsequently added [³H]PteGlu by twice as much as did preincubation with methotrexate, suggesting that methotrexate may only partly share the uptake mechanism for [³H]PteGlu. [³H]PteGlu uptake was not affected by preincubation with diphenylhydantoin or a sulphydryl inhibitor. Uptake of [³H‐CH₃]H₄PteGlu by human bone marrow cells appeared to be approximately twice the uptake of [³H]PteGlu. The findings support the concept of two mechanisms for folate uptake by human reticulocytes and bone marrow cells: an energy‐dependent, active carrier mechanism probably of primary physiologic significance, and a seemingly passive diffusion‐like mechanism, probably primarily of pharmacologic significance.