title: Thymidine-modulated 5-fluorouracil metabolism in liver and RIF-1 tumors studied by 19F magnetic resonance spectroscopy.
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 alpha-fluoro-beta-ureidopropionic acid and alpha-fluoro-beta-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 alpha-fluoro-beta-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 less than .1 and P less than .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 less than .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 less than .0001, both).
authors.affiliation: MR Research Center, Cleveland Clinic Foundation, OH 44195.
authors.forename: P E
authors.initials: PE
authors.lastname: Sijens
authors.forename: T C
authors.initials: TC
authors.lastname: Ng
mesh_terms: D000818:Animals; D002460:Cell Line; D005260:Female; D005354:Fibrosarcoma / Q000209:etiology / Q000378:metabolism*; D005472:Fluorouracil / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008809:Mice, Inbred C3H; D009381:Neoplasms, Radiation-Induced / Q000378:metabolism*; D013936:Thymidine / Q000494:pharmacology*
chemical_list: D005472:Fluorouracil; D013936:Thymidine