Triamterene is a diuretic with activity in vitro as a folic acid antagonist inhibiting dihydrofolate reductase. Megaloblastosis ifi patients on triamterene was suspected to be due to inhibition of DNA synthesis secondary to triamterene inhibition of dihydrofolate reductase. We studied the effect of triamterene on nucleic acid synthesis with the use of L1210 mouse ascites leukemia. Cells were harvested 5 days after intraperitoneal inoculation of 2 x 105 cells and the incorporation of 14C-thymidine (TdR), 3H-deoxyuridine (UdR), or 14C-uridine (UR) was measured. In vitro triamterene (10-1 μM per milliliter) resulted in 40 per cent suppression of UdR incorporation into DNA as compared to 73 per cent suppression with methotrexate in the same concentration. Triamterene minimally inhibited and methotrexate moderately stimulated TdR into DNA. Neither triamterene nor methotrexate influenced UR incorporation into RNA. In contrast to methotrexate, in vivo treatment of ascites mice with triamterene showed no inhibition of UdR incorporation. The lack of triamterene effect on DNA synthesis in vivo suggests rapid dissociation of drug-enzyme complex in vivo, which would be desirable for a diuretic nonmyelosuppressive action
