Effects of folates and products of folate metabolism on proliferation of human leukemia cell line K562 in culture

Human leukemia cell K562 in culture displayed an absolute requirement for folate, proliferating at optimal rate only when the total intracellular folate concentration was greater than 1.5 uM. This critical intracellular concentration was maintained by extracellular 5-formyltetrahydrofolic acid or 5-methyltetrahydrofolic acid at a 100-fold lower concentration than folic acid. Growth rate of folate-deficient cells was proportional to intracellular concentration of fully-reduced, non-methylated folate but not to intracellular 5-methyltetrahydrofolate concentration. Growth of folate-deficient cells was stimulated by inosine but not by thymidine, suggesting that the primary cause of growth restriction in these cells was purine deficiency. Serine stimulated, and glycine inhibited, growth of K562 cells, likely by modulating the supply of one-carbon units for folate metabolism. Folate-deficient cells were larger in size than folate-replete cells, but megaloblastic morhology was not observed. DNA content of folate-deficient cells was predominantly characteristic of cells in S or G2/M phases of the cell cycle