Cytosine deaminase gene as a potential tool for the genetic therapy of colorectal cancer

J Surg Oncol. 1996 Jan;61(1):42-8. doi: 10.1002/(SICI)1096-9098(199601)61:1<42::AID-JSO10>3.0.CO;2-Z.


The bacterial enzyme cytosine deaminase (CD) catalyzes the conversion of 5-fluorocytosine (5-FC) to the lethal 5-fluorouracil (5-FU) and so provides a useful system for selective killing of gene-modified mammalian tumor cells. Cloning of the CD gene from Escherichia coli and expression in human tumor cell lines enabled these cells to convert 3H-labeled 5-FC into 3H-5-FU. Two CD-expressing human tumor cell lines (adenocarcinoma cell line KM12 and glioblastoma cell line T1115) became 200-fold more sensitive to 5-FC than the nonexpressing parental cell lines. At least 90% of the cells are killed within 7 days. CD-expressing cells are able to kill nonexpressing cells when grown in the same culture flask (bystander effect). The CD gene may be used as a suicide system for in situ chemotherapy or as a safety mechanism abrogating the expression of other genes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Cell Death
  • Cloning, Molecular
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / therapy*
  • Cytosine Deaminase
  • Escherichia coli / enzymology*
  • Escherichia coli / genetics
  • Flucytosine / pharmacology
  • Fluorouracil / pharmacology
  • Genetic Therapy*
  • Genetic Vectors
  • Glioblastoma / pathology
  • Humans
  • Interleukin-2 / metabolism
  • Molecular Sequence Data
  • Nucleoside Deaminases / genetics*
  • Polymerase Chain Reaction
  • R Factors
  • Transfection
  • Tumor Cells, Cultured


  • Interleukin-2
  • Flucytosine
  • Nucleoside Deaminases
  • Cytosine Deaminase
  • Fluorouracil