Studies on mechanisms of 5-fluorouracil resistance in murine and human tumors

B. Ardalan, J. S. MacDonald, D. Cooney, P. S. Schein

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


An in vitro cell free assay system to measure phosphorylated products of 5-Fluorouracil is described. Total phosphorylated products and mono-, di and triphosphates of 5-Fluorouracil are measured along with the rate of fluorodeoxyuridylate generation. This assay has been applied to ten murine tumors and eight biopsy specimens from human breast adenocarcinomas. Phosphorylation patterns have been examined in murine tumors demonstrating in vivo sensitivety or resistance to 5-Fluorouracil. There are distinct differences in the patterns of phosphorylation between sensitive and resistant tumors. I a 5-Fluorouracil sensitive murine tumor, mono-, di and triphosphates are produced. In a resistant tumor only monophosphates are produced. Cell free supernatants from human breast tumors produce less total phosphorylation than murine tumors and some specimens produce only monophosphates whereas others produce mono-, di and triphosphates. Human tumors are in general more efficient producers of fluorodeoxyuridylate than murine tumors. These data suggest that resistance to 5-Fluorouracil may correlate with decreased concentration of di and triphosphates of 5-Fluorouracil in some murine tumors. Further experiences are required to demonstrate the value of this easily performed assay system in predicting clinical response to 5-Fluorouracil in man.

Original languageEnglish (US)
Pages (from-to)55-59
Number of pages5
JournalBulletin du Cancer
Issue number1
StatePublished - Jan 1 1979
Externally publishedYes

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research


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