Molecular Pharmacology, Vol 6, 273-280, Copyright © 1970 by the American Society for Pharmacology and Experimental Therapeutics

Fluorinated Pyrimidines

XXXVII. Effects of 5-Trifluoromethyl-2'-deoxyuridine on the Synthesis of Deoxyribonucleic Acid of Mammalian Cells in Culture

¹ McArdle Laboratory for Cancer Research, University of Wisconsin, Madison, Wisconsin 53706

5-Trifluoromethyl-2'-deoxyuridine (F₃TdR), a thymidine analogue, is incorporated into the DNA of HeLa and leukemia L5178Y cells in culture. Under conditions of synchrony induced by the production of thymidine deficiency and rescue by thymidine or a thymidine analogue, the addition of F₃TdR does not permit any cell division, in contrast to thymidine, 5-bromo-2'-deoxyuridine, or 5-iodo-2'-deoxyuridine, which support cell division. However, F₃TdR is incorporated into the cellular DNA, but to only about one-fourth the extent of thymidine. Alkaline sucrose gradient sedimentation revealed that the molecules of DNA containing F₃TdR are smaller than normal DNA, suggesting that the rate of growth or joining of chains of DNA is inhibited as a result of the incorporation of the analogue.

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ACKNOWLEDGMENT We are grateful to Mrs. Barbara Lindsey for skilled technical assistance.