in vitro and in vivo Cytotoxic Effect of Adenovirus-Mediated Cytosine Deaminase Gene Transfer on Murine Melanoma
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Abstract:
Escherichia coli cytosine deaminase ( CD) gene was transfected into murine B16F10 melanoma cells by recombinant adenovirus AdCD in vitro . The tumor cells infected with AdCD were more sensitive to 5-fluorocytosine (5FC) than cells infected with a control adenovirus AdLacZ. The supernatant from B16F10 cells treated with AdCD/5FC was transferred to uninfected cells, and we found that only 6. 25 % of the supernatant could significantly inhibit the growth of wild type B16F10 cells. When AdCD was directly injected into established subcutaneous B16F10 tumors in mice followed by intraperitoneal injection of 5FC for 10 days, a significant reduction in tumor size and prolongation of survival period were observed. These studies not only explored the cytotoxic effects of AdCD/5FC on B16F10 melanoma cells in vitro and in vivo but also elucidated the mechanisms of its bvstander effect.