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Induction of Tumor Cell Apoptosis by Adenovirus-Mediated E. coli Cyto-sine Deaminase Gene Transfection and Its Bystander eftect
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Abstract:
Adenoviruses harboring E. coli cytosine deaminase gene (AdCD) were used to transfect murine FBL-3 ery-throleukemia cells in vitro. FBL3 cells infected with AdCD were more sensitive to 5-fluorocytosine (5-FC) than cells infected with a control adenovirus AdLacZ. Further study indicated that this combination therapy (AdCD and 5-FC) killed tumor cells by inducing apoptosis of FBL-3 cells. The supematants from FBL-3 cells treated with AdCD/5-Fc were transferred on the culture system of uninfected (wild - type) FBL-3 cells, the result indicated that only 6.25% of the supernatant could induce significant cytotoxicity on wild type FBL3 cells. The results demonoustrated that bystander effect plays an important role in AdCD-mediated cytotoxicities. Direct injection of AdCD into established subcutaneous FBL3 tumor in mice followed by daily intraperitoneal injection of 5-FC for 10 days was found to inhibit tumor growth significant-
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