title: Effects of hyperthermia on the metabolism of 5-fluorouracil in vitro.
abstract: The effects of hyperthermia (38-42 degrees C) on the metabolism of 5-fluorouracil (5-FU) were examined using Ehrlich tumour cells (E-cells) and Sarcoma-180 cells (S-180 cells) in vitro. A temperature-dependent elevation of the intracellular concentration of 5-FU was observed in both types of tumour cell after incubation with 5-FU. The levels of 5-fluorouridine (FUR) and 5-fluoro-2'-deoxyuridine (FdUR), which are active metabolites of 5-FU, increased significantly after treatment of cells with 5-FU and hyperthermia. The highest concentrations of these active metabolites were found when the cells were incubated at 39 degrees C. The levels of alpha-fluoro-beta-ureido-propionic acid (FUPA) and F-beta-alanine, which are inactive catabolic metabolites of 5-FU, also increased when the cells were incubated at 39 degrees C. The percentage inhibition of thymidilate synthetase (TS) activity remained high (about 60-70%) at 39 degrees C for 240 min. These results suggest that the optimal temperature for potentiating the intracellular metabolism of 5-FU, in terms of both activation and inactivation, is 39 degrees C in vitro.
authors.affiliation: First Department of Surgery, Tottori University School of Medicine, Yonago, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Maeta
authors.forename: T
authors.initials: T
authors.lastname: Sawata
authors.forename: N
authors.initials: N
authors.lastname: Kaibara
mesh_terms: D000818:Animals; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy / Q000378:metabolism / Q000628:therapy; D003131:Combined Modality Therapy; D005467:Floxuridine / Q000378:metabolism; D005472:Fluorouracil / Q000378:metabolism* / Q000627:therapeutic use; D006979:Hyperthermia, Induced; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D012510:Sarcoma 180 / Q000188:drug therapy / Q000378:metabolism / Q000628:therapy; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors; D014508:Urea / Q000031:analogs & derivatives / Q000378:metabolism; D014529:Uridine / Q000031:analogs & derivatives / Q000378:metabolism; D015091:beta-Alanine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D005467:Floxuridine; D015091:beta-Alanine; C032348:alpha-fluoro-beta-alanine; C001943:5-fluorouridine; C045635:alpha-fluoro-beta-ureidopropionic acid; D014508:Urea; D013940:Thymidylate Synthase; D005472:Fluorouracil; D014529:Uridine