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Quantitative Studies of Incorporation of Exogenous Thymidine and 5-Bromodeoxyuridine into Deoxyribonucleic Acid of Mammalian Cells in Vitro^*

Joseph P. Kriss and Lászlò Révész

( Departments of Medicine and Radiology, Stanford University School of Medicine, Stanford, California)

Methods for the synthesis of bromodeoxyuridine-Br⁸² and bromodeoxyuridine-H³ (BUdR) are described.

The incorporation of both thymidine and BUdR into the deoxyribonucleic acid (DNA) of rat bone marrow cells in vitro was markedly influenced by concentrations of thymidine and BUdR, respectively, in the incubation media. At equivalent concentrations of respective substrate, the amount of thymidine incorporated always exceeded that of BUdR. Limiting concentrations of both thymidine and BUdR were found, above which little or no further incorporation of the respective compounds occurred. Efficiency of incorporation of each compound, as measured by percentage of the available dose which was incorporated, was highest at low respective substrate concentrations.

The rates of incorporation of thymidine and BUdR into the DNA of Ehrlich ascites tumor cells in vitro were maximal at the beginning of incubation and fell progressively thereafter.

Thymidine and BUdR mutually inhibit the incorporation of the other into DNA. Evidence is presented that this inhibition may be due to competition by the compounds for binding sites on the same enzyme, which is rate-limiting for their entry into the cell and subsequent incorporation into DNA.

The presence of 5-fluorouracil in the medium exerts an enhancing effect on thymidine and BUdR incorporation.

^* This investigation was supported by grant CY-4096 from the National Cancer Institute, National Institutes of Health, U.S. Public Health Service, Bethesda, Md.

On leave from Institute for Tumor Biology, Karolinska Instituted Stockholm, Sweden.

WITH THE TECHNICAL ASSISTANCE OF LUCIE TUNG AND SUSAN EGLOFF

Received 3/27/61.