1. Cytosine deaminase gene as a potential tool for the genetic therapy of colorectal cancer
- Author
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Franz Oberdorfer, Johannes Gebert, Ulrich Moebius, Marcus Lindauer, Uwe Haberkorn, Christian Herfarth, H. K. Schackert, and Simon Rowley
- Subjects
Colorectal cancer ,Genetic enhancement ,R Factors ,Genetic Vectors ,Molecular Sequence Data ,Flucytosine ,Nucleoside Deaminases ,Biology ,medicine.disease_cause ,Transfection ,Polymerase Chain Reaction ,Cytosine Deaminase ,Bystander effect ,medicine ,Escherichia coli ,Tumor Cells, Cultured ,Humans ,Cloning, Molecular ,Gene ,Cloning ,Base Sequence ,Cell Death ,Cytosine deaminase ,General Medicine ,Genetic Therapy ,medicine.disease ,Oncology ,Cell culture ,Immunology ,Cancer research ,Interleukin-2 ,Surgery ,Fluorouracil ,Colorectal Neoplasms ,Glioblastoma - Abstract
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. © 1996 Wiley-Liss, Inc.
- Published
- 1996