Abstract
19F Magnetic resonance spectroscopy was used to study the impact of the biochemical modulator thymidine (TdR) on the 5-fluorouracil (5FU) metabolism in the livers and radiation-induced fibrosarcoma (RIF-1) tumors of 5FU-treated C3H mice. The liver spectra measured after administration of 5FU (65 or 130 mg/kg IP) showed the 5 FU resonance and its catabolites α-fluoro-gb-ureidopropionic acid and α-fluoro-β-alanine. At the latter dose, fluoronucleotide signal was also detected. The liver spectra of TdR-pretreated (500 mg/kg, IP) mice showed additional signals of fluoronucleotide and fluoronucleoside at both 5FU doses, while α-fluoro-β-alanine was not detected. TdR pretreatment increased the half-life of 5FU in livers from 24 ± 2 to 126 ± 46 SEM min at the 5FU dose of 65 mg/kg and from 28 ± 2 to 95 ± 22 min at the 130 mg/kg dose ( P < .1 and P < .01, respectively). TdR-pretreated mice had higher 5FU anabolite (fluoronucleotide + fluoronucleoside) levels in their RIF-1 tumors than nonpretreated mice that received the same 5FU doses (56 ± 15 SEM vs. 0 arbitrary units at the 5FU dose of 65 mg/kg, and 88 ± 21 vs. 10 ± 3 arbitrary units at 130 mg/kg 5FU; P < .0001). The percentage drop in tumor volume was enhanced in the mice that received TdR, from 27 ± 4 SEM to 52 ± 2 at the 5 FU dose of 65 mg/kg and from 24 ± 3 to 65 ± 4 at the 130-mg/kg dose ( P < .0001, both).
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