Cytosine arabinoside and Methotrexate alter in different ways the metabolic patterns of leukocytes from patients with acute granulocytic leukemia. The variations in the incorpora tion into DNA of deoxyuridine and thymidine during the first twenty-four hours after cytosine arabinoside administration

Cytosine arabinoside and Methotrexate alter in different ways the metabolic patterns of leukocytes from patients with acute granulocytic leukemia. The variations in the incorpora tion into DNA of deoxyuridine and thymidine during the first twenty-four hours after cytosine arabinoside administration were correlated with one another but not with the variation in activity of thymidylate synthetase, thymidine kinase, or uri dine kinase. The activity of these three enzymes varied as a related unit. Dihydrofolate reductase activity varied indepen dently of the other five parameters. The response of these parameters to cytosine arabinoside varied from stimulation for some patients to inhibition of activity in others. After the administration of Methotrexate, an inhibition of dihydrofolate reductase was observed, but this was not correlated with the inhibition of deoxyuridine or the general stimulation of thymi dine incorporation into DNA nor to a general variation in the activity of thymidine kinase and unidine kinase. A correlation after Methotrexate administration was observed between the inhibition of deoxyuridine incorporation into DNA and a stim ulation of thymidylate synthetase activity. A dissociation was observed after Methotrexate administration of the relationship between thymidylate synthetase, thymidine kinase, and uri dine kinase which followed cytosine arabinoside administra tion.