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HA Ingraham, BY Tseng and M Goulian
Intracellular pools of 5-fluoro-2'-deoxyuridine (FdUrd) and dUrd nucleotides were measured in cultured human lymphoblasts treated with FdUrd. At 1 microM FdUrd, intracellular 5-fluoro-2'-deoxyuridine 5'- monophosphate (FdUMP) was approximately 400 pmoles/10(6) cells, and FdUTP was approximately 0.1 pmole/10(6) cells. Intracellular dUMP and dUTP were elevated to values of approximately 1000 pmoles/10(6) cells and approximately 0.1 pmol/10(6) cells, respectively. With decrease in dTTP levels, utilization of FdUTP and dUTP as substrates for DNA synthesis became significant. FdUMP and dUMP, approximately 5 pmoles of each per micromole of DNA nucleotide, were found in DNA of cells treated with FdUrd (1 microM). The active removal of FUra and Ura from DNA of FdUrd-treated cells by the normal repair mechanism may lead to fragmentation of DNA and contribute to the cytotoxic effect of FdUrd.
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