Studies on the Uptake of Synthetic Conjugated Folates by Human Marrow Cells

Pteroyltriglutamate shows little abiility (between 1% and 5%), compared to pteroylmonoglutamate (folic acid), to enter human marrow cells and to act as a coenzyme in intracellular DNA synthesis. This was shown by comparing the effectiveness of these two forms of the vitamin at stimulating folate-dependent pyrimidine incorporation into DNA in vitro in the bone marrow cells and lymphocytes of patients with megaloblastic anemia. It, therefore, appears that human hemopoietic cells (like Streptococcus fecalis rather than Lactobacillus casei) are unable to take up efficiently polyglutamyl forms of folate. The suggestion that polyglutamyl analogues of the antifolates might be more effective chemotherapeutic agents than corresponding monoglutamates, while biochemically possible, would appear to be precluded because of failure of transport of these compounds into human hemopoietic cells.