Pyrimidine metabolism in human leukocytes. I. Contribution of exogenous thymidine to DNA-thymine and its effect on thymine nucleotide synthesis in leukemic leukocytes.

The pathways for the formation of DNA-thymine from syn thesis de novo and from exogenous thymidine (TdR) have been studied in intact leukocytes from patients with chronic myelogenous leukemia. The most significant observations were as follows: (a) DNA-thymine derived from exogenous TdR in creases from 13% to 87% over a range of TdR concentrations from 0.03 /¿Mto 300 /XM.(b) TdR causes expansion of the total thymidine diphosphate and thymidine triphosphate (TTP) pool but does not influence the contribution of the pathway de novo to this pool. Thus, the increasing contribution of exogenous TdR to the formation of DNA-thymine occurs be cause of a progressive dilution of TTP synthesized de novo with TTP derived from exogenous TdR. (c) In concentrations greater than 0.3 /¿M, TdR inhibits DNA synthesis but not RNA synthesis. This inhibition is dependent on the continued presence of TdR in the medium and is reversed by the addition of deoxycytidine.