Differences in metabolism of 5-fluorouracil and 5-fluorouridine and regulation by glucosamine in human colon cancer multicell tumor spheroids
✍ Scribed by Tong-Bin Chen; Zěljko Bajzer; Slobodan Macura; Stanimir Vuk-Pavlović
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 171 KB
- Volume
- 12
- Category
- Article
- ISSN
- 0952-3480
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✦ Synopsis
Glucosamine (GlcN)
modulates fluoropyrimidine metabolism and enhances cytotoxicity of 5fluorouridine (FUrd), but not of 5-fluorouracil (FUra), in human tumor models. To elucidate the underlying metabolic differences between FUra and FUrd, by the use of 19 F and 31 P NMR spectroscopy we studied these drugs in multicell tumor spheroids (MTS) formed by human colon carcinoma cells HT-29. This experimental system allowed detailed kinetic measurements of anabolic intracellular phosphates and fluorophosphates over periods of up to 2 days. Timedependent NMR data were reduced and interpreted by the use of nonlinear compartmental models which yielded numerical values for the empirical rate constants characterizing mass transfer among the compartments. An analysis of these rate constants indicated qualitative and quantitative differences in the metabolism of FUra and FUrd and in the effects of GlcN on these drugs. The enhanced generation of FUDP-hexoses was a predicted effect of GlcN, but inhibited formation of fluorouridine diphosphates and fluorouridine triphosphates in FUra-treated MTS, and the magnitude of stimulation of fluoropyrimidine incorporation into macromolecules in FUrd-treated MTS were not predicted.