Nucleotide levels and incorporation of 5-fluorouracil and uracil into DNA of cells treated with 5-fluorodeoxyuridine.
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.
D004247:DNA / Q000096:biosynthesis*; D003854:Deoxyribonucleotides / Q000378:metabolism; D005467:Floxuridine / Q000378:metabolism*; D005472:Fluorouracil / Q000378:metabolism*; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism; D014498:Uracil / Q000378:metabolism*; D014500:Uracil Nucleotides / Q000378:metabolism
D003854:Deoxyribonucleotides; D014500:Uracil Nucleotides; D005467:Floxuridine; D014498:Uracil; D004247:DNA; D005472:Fluorouracil