Effects of trimethoprim on leukaemic cells in vitro.

Trimethoprim-Sulfamethoxazole (TMP-SMZ) is a fixed combination of antibiotics which is widely used for prophylaxis and treatment of infections in patients undergoing cancer chemotherapy. TMP has been reported to inhibit growth of haemopoietic stem cells in vitro. If TMP-SMZ inhibits leukaemic cell growth, it could interfere with antileukaemic treatment, especially with S phase specific agents. TMP-SMZ at a concentration of 10 micrograms/ml (TMP) produced 50% inhibition of incorporation of 3H-deoxyuridine in DNA of L1210 and human lymphoblastic leukaemia cell. TMP-SMZ (1 g/ml TMP) produced 30% prolongation of doubling time of L1210 in vitro. Pure TMP (10 micrograms/ml) but not SMZ (50 micrograms/ml) produced the same effect as TMP-SMZ. Cell inhibitory effects could be completely reversed by folinic acid. These findings suggest that TMP produces some degree of inhibition of dihydrofolic acid reductase in mammalian cells and can potentially influence the effects of chemotherapy on tumour and/or host cells.