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Transfection of murine fibroblast cells with human cytidine deaminase cDNA confers resistance to cytosine arabinoside.

Authors
  • Momparler, R L
  • Laliberté, J
  • Eliopoulos, N
  • Beauséjour, C
  • Cournoyer, D
Type
Published Article
Journal
Anti-Cancer Drugs
Publisher
Ovid Technologies (Wolters Kluwer) - Lippincott Williams & Wilkins
Publication Date
May 01, 1996
Volume
7
Issue
3
Pages
266–274
Identifiers
PMID: 8791999
Source
Medline
License
Unknown

Abstract

One of the major limitations in the use of cytosine arabinoside (Ara-C) in cancer chemotherapy is the hematopoietic toxicity produced by this nucleoside analog. One approach to overcome this problem would be to insert a gene for drug resistance to Ara-C in normal hematopoietic cells to protect them from drug toxicity. An interesting candidate gene for this aim is cytidine deaminase which catalyzes the deamination of Arac-C, resulting in a significant loss of its antineoplastic activity. We have ligated the human cDNA for cytidine deaminase into the plasmid vector pMFG. Transfection of NIH 3T3-derived GP + E86 murine fibroblasts cells with this vector resulted in a marked increase (> 50-fold) in the expression of cytidine deaminase. In addition, the transfected cells showed resistance to the cytotoxic action and to the inhibition of DNA synthesis produced by Ara-C. Northern and Western blot analysis of the transfected cells showed increased expression of mRNA for cytidine deaminase and increased immunologically detectable enzyme. The ability to confer drug resistance to Ara-C through gene transfer of cytidine deaminase may have the potential as a selectable marker and for the protection of the bone marrow from the toxicity produced by this analog so as to increase its effectiveness in cancer chemotherapy.

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