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Cytosine deaminase gene as a potential tool for the genetic therapy of colorectal cancer
Author(s) -
Rowley Simon,
Lindauer Marcus,
Gebert Johannes F.,
Haberkorn Uwe,
Oberdorfer Franz,
Moebius Ulrich,
Herfarth Christian,
Schackert HansKonrad
Publication year - 1996
Publication title -
journal of surgical oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.201
H-Index - 111
eISSN - 1096-9098
pISSN - 0022-4790
DOI - 10.1002/(sici)1096-9098(199601)61:1<42::aid-jso10>3.0.co;2-z
Subject(s) - cytosine deaminase , suicide gene , cell culture , cancer research , bystander effect , gene , genetic enhancement , microbiology and biotechnology , cytidine deaminase , cell , cancer , biology , medicine , genetics , immunology
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 3 H‐labeled 5‐FC into 3 H‐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.