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Coordinated Changes in Thymidine 5'-Monophosphate Metabolism of Leukocytes following Vincristine Administration to Patients with Acute Granulocytic Leukemia¹

Laboratories of Pharmacology, Children's Cancer Research Foundation, and Departments of Pathology and Medicine, Harvard University Medical School, Boston, Massachusetts 02115

The effect of vincristine on thymidine and deoxyuridine incorporation into DNA and on thymidylate synthetase, thymidine kinase, uridine kinase, and dihydrofolate reductase activities of leukocytes from patients with acute granulocytic leukemia was examined at 1, 4, 24, and 48 hours after drug administration. Relative to the pretreatment level of activity, an elevation was frequently observed at the two earlier time points, and after 24 and 48 hours there was frequently a depression. The changes in deoxynucleoside incorporation into DNA and in thymidylate synthetase and dihydrofolate reductase activities were correlated with one another, P < 0.01. Thymidine kinase and uridine kinase changed as a unit, P < 0.01, but independently of the other four parameters, P > 0.05.

The correlation between changes in metabolic patterns of patients with acute granulocytic leukemia after vincristine contrasts with the lack of correlation seen between patients prior to therapy. However, there is a strong similarity between the pattern seen in patients with acute granulocytic leukemia treated with vincristine and the pattern of relationships observed for patients with untreated acute lymphocytic leukemia.

¹ These studies were supported in part by Contract PH 43-66-541 from the Cancer Chemotherapy National Service Center, and Research Grant C6516 from the National Cancer Institute, NIH.

² Reprint requests should be directed to this author at St. Jude Children's Research Hospital, 332 N. Lauderdale, Memphis, Tennessee 38101.

Received 8/29/68. Accepted 11/24/68.