Cytosine deaminase gene as a potential tool for the genetic therapy of colorectal cancer.
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.
Rowley
S
S
Surgery Clinic, University of Heidelberg, Germany.
Lindauer
M
M
Gebert
J F
JF
Haberkorn
U
U
Oberdorfer
F
F
Moebius
U
U
Herfarth
C
C
Schackert
H K
HK
D001483:Base Sequence; D016923:Cell Death; D003001:Cloning, Molecular; D015179:Colorectal Neoplasms / Q000473:pathology / Q000628:therapy*; D043525:Cytosine Deaminase; D004926:Escherichia coli / Q000201:enzymology* / Q000235:genetics; D005437:Flucytosine / Q000494:pharmacology; D005472:Fluorouracil / Q000494:pharmacology; D015316:Genetic Therapy; D005822:Genetic Vectors; D005909:Glioblastoma / Q000473:pathology; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D008969:Molecular Sequence Data; D009700:Nucleoside Deaminases / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011815:R Factors; D014162:Transfection; D014407:Tumor Cells, Cultured
D007376:Interleukin-2; D005437:Flucytosine; D009700:Nucleoside Deaminases; D043525:Cytosine Deaminase; D005472:Fluorouracil