Enhanced therapeutic efficacy of 5'deoxy-5-fluorouridine in 5-flourouracil resistant head and neck tumours in relation to 5-fluorouracil metabolizing enzymes

G. J. Peters, B. J M Braakhuis, E. A. De Bruijn, E. J. Laurensse, M. Van Walsum, H. M. Pinedo

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

Four human head and neck xenograft (HNX) tumour lines grown in nude mice and two murine colon carcinomas (Colon 26 and 38) were tested for their sensitivity to 5-fluorouracil (5-FU) and its prodrug 5'deoxy-5-fluorouridine (Doxifluridine, 5'd-FUR). 5-FU sensitivity at the maximum tolerated dose (MTD) showed the following pattern: HNX-DU <HNX-KE=HNX-E=HNX-G <Colon 26 > HNX-DU > HNX-G > HNX-E > HNX-KE >> Colon 38; of 5-FU to FdUMP via FUdR: Colon 26 > HNX-DU=HNX-KE > HNX-E > HNX-G=Colon 38; and that of 5-FU to FUMP catalysed by orotate phosphoribosyl transferase (OPRT); Colon 26 ≥ Colon 38 > HNX-KE > HNX-E=HNX-DU=HNX-G. Only those tumours with a relatively high activity of OPRT were sensitive to 5'd-FUR. Colon 26, which has a very high rate of pyrimidine nucleoside phosphorylase, showed a relatively high increase in the therapeutic efficacy. It is concluded that a low rate of pyrimidine nucleoside phosphorylase is enough to convert 5'd-FUR to 5-FU; further anabolism of 5-FU catalysed by OPRT may be limiting and explain the differential sensitivity.

Original languageEnglish (US)
Pages (from-to)327-334
Number of pages8
JournalBritish Journal of Cancer
Volume59
Issue number3
StatePublished - 1989
Externally publishedYes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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