TY - JOUR T1 - Nucleotide levels and incorporation of 5-fluorouracil and uracil into DNA of cells treated with 5-fluorodeoxyuridine. JF - Molecular Pharmacology JO - Mol Pharmacol SP - 211 LP - 216 VL - 21 IS - 1 AU - H A Ingraham AU - B Y Tseng AU - M Goulian Y1 - 1982/01/01 UR - http://molpharm.aspetjournals.org/content/21/1/211.abstract N2 - 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. ER -