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Molecular Pharmacology, Vol 6, 251-254, Copyright © 1970 by the American Society for Pharmacology and Experimental Therapeutics

Thymidine Kinase as a Determinant of the Response to 5-Fluoro-2'-deoxyuridine in Transplantable Murine Leukemias

DAVID KESSEL 1 and ISIDORE WODINSKY 1

1 Department of Pharmacology, University of Rochester School of Medicine, Rochester, New York 14620, and Arthur D. Little Corporation, Cambridge, Massachusetts 02140

The responsiveness to 5-fluoro-2'-deoxyuridine of different transplantable mouse leukemias in vivo was inversely correlated with tumor cell levels of thymidine kinase (EC 2.7.1.21). This enzyme transforms the drug to the pharmacologically active nucleotide 5-fluoro-2'-deoxyuridylic acid. However, it also provides an alternative pathway for circumventing time drug-induced blockade of thymidylate biosynthesis.

Note:
ACKNOWLEDGMENTS Technical assistance was provided by Regina Bruns (at the University of Rochester) and Albert Ross (at Arthur D. Little Corporation).

Submitted on October 24, 1969






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