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

✍ Scribed by Rowley, Simon; Lindauer, Marcus; Gebert, Johannes F.; Haberkorn, Uwe; Oberdorfer, Franz; Moebius, Ulrich; Herfarth, Christian; Schackert, Hans-Konrad

Publisher: John Wiley and Sons
Year: 1996
Tongue: English
Weight: 632 KB
Volume: 61
Category: Article
ISSN: 0022-4790
DOI: 10.1002/(sici)1096-9098(199601)61:1<42::aid-jso10>3.0.co;2-z

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✦ Synopsis

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 Escherichiu coli and expression in human tumor cell lines enabled these cells to convert 'H-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.

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