Assignment and pH dependence of the 19F-NMR resonances from the fluorouracil anabolites involved in fluoropyrimidine chemotherapy.
Fluoropyrimidine chemotherapy relies on the intracellular anabolic conversion of 5-fluorouracil and the corresponding nucleosides to cytotoxic fluorinated nucleotides (F-Nuctd), such as 5-fluorouridine-5'-triphosphate (FUTP) or 5-fluoro-2'-deoxyuridine-5'-monophosphate (FdUMP), which can be detected by 19F-NMR spectroscopy. We have made 19F-NMR signal assignments at 11.7 T and 4 degrees C for model solutions containing 5-fluorouracil (FUra), 5-fluorouridine (FUrd), 5-fluoro-2'-deoxyuridine (FdUrd), 5-fluorouridine-5'-monophosphate (FUMP), FdUMP, 5-fluorouridine-5'-diphosphate (FUDP), FUTP and 5-fluorouridine-5'-diphospho(1)-alpha-D-glucose (FUDPG), and we have studied the effects of pH over the range 4.5-7.8, of Mg2+ concentration and addition of EDTA. This information provides a basis for the analysis of 19F-NMR spectra obtained from cells, tissues or extracts following fluoropyrimidine treatment.
Central Spectroscopy Department, German Cancer Research Center, Heidelberg.
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NW
Lutz
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Hull
D000970:Antineoplastic Agents / Q000378:metabolism*; D005472:Fluorouracil / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008274:Magnesium / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D014544:Uridine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism
D000970:Antineoplastic Agents; C025635:5-fluorouridine 5'-triphosphate; D008274:Magnesium; D005472:Fluorouracil; D014544:Uridine Triphosphate