Bystander effect from cytosine deaminase and uracil phosphoribosyl transferase genes in vitro: A partial contribution of gap junctions |
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| Authors: | Toshiaki Tanaka,Agnè s Duflot-Dancer,Michè le Tiraby,Colette Piccoli,Gé rard Tiraby,Hiroshi Yamasaki,Marc Mesnil |
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| Affiliation: | 1. Unit of Multistage Carcinogenesis, International Agency for Research on Cancer, 150 cours Albert Thomas, 69375 Lyon cedex 08, France;2. InvivoGen, 3950 Sorrento Valley Blvd Suite A, San Diego, CA 92121, USA;3. Laboratoire de Microbiologie et Génétique Appliquées, CNRS, Université Paul Sabatier, 118 route de Narbonne, 31062 Toulouse cedex, France;4. Institute of Cellular Physiology and Biology, UMR CNRS 6187, University of Poitiers, 40 Avenue Pineau, 86022 Poitiers, France |
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| Abstract: | Among gene therapy strategies elaborated to kill cancer cells, one uses the CodA gene, coding for cytosine deaminase (CD) that converts 5-fluorocytosine (5-FC) into toxic 5-fluorouracil (5-FU). To enhance 5-FC metabolic activation, we prepared a vector carrying CodA and upp (uracil phosphoribosyl transferase) genes which rendered HeLa cells sensitive to 5-FC and enhanced a bystander effect not mediated by gap junctions. However, 1% CD+–UPP+ cells were able to kill 40% of the cell population if the cells were communicating. This suggests that, at very low percentages of CD+–UPP+ cells, CodA and upp induce a bystander effect through gap junction-dependent mechanisms. |
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| Keywords: | CD, cytosine deaminase CodA, cytosine deaminase gene Cx, connexin 5-FC, 5-fluorocytosine 5-FU, 5-fluorouracil GJIC, gap junctional intercellular communication upp, uracil phosphoribosyl transferase |
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