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Pyrimidine Metabolism in Human Leukocytes

II. Metabolism of the Thymine Nucleotide Pools in Normal and Leukemic Leukocytes

Medicine Branch and Laboratory of Physiology, National Cancer Institute, NIH, Bethesda, Maryland

The incorporation of thymidine (TdR)-³H into the thymidine diphosphate (TDP) and thymidine triphosphate (TTP) pools of intact leukocytes from normal donors and patients with chronic myelogenous leukemia (CML) reached a maximum within 5 min at 37°C. A steady state was maintained during the subsequent 20 min. The time to reach maximal incorporation of TdR-³H into the thymidine monophosphate (TMP) pool was slower than into the TDP and TTP pools. In leukemic cells the rate of equilibration of TMP with TdR-³H was related directly to the TdR concentration and inversely to the temperature.

With increasing concentrations of TdR, expansion of the TMP pool derived from TdR was greater than expansion of the TDP and TTP pools. In leukemic leukocytes the TDP and TTP pools were approximately equal in size and accounted for 65% of the thymine nucleotides in the presence of 1 µM TdR but only 10% in the presence of 300 µM TdR. In normal leukocytes at these TdR concentrations the TDP and TTP pools accounted for 35% and 5% of the total thymine nucleotides.

Over the range of TdR concentrations studied, incorporation of TdR-³H into the TMP pool was 2- to 5-fold greater and incorporation into the TDP and TTP pool was 6- to 15-fold greater in CML than in normal leukocytes. Incorporation of 3 µM TdR-³H into DNA was 30-fold greater in CML than in normal leukocytes.

In the presence of TdR at a concentration of 14 µM the turnover rate of the thymine nucleotide pools was 3 min. Approximately 35% of the TTP turnover was due to its incorporation into DNA.

¹ Present address: II and IV (Harvard) Medical Service, Boston City Hospital, Boston, Mass.

² To whom requests for reprints should be addressed at the Laboratory of Physiology, National Cancer Institute, NIH, Bethesda, Md.

Received 1/28/66. Accepted 5/24/66.