Tanaka Toshiaki, Duflot-Dancer Agnès, Tiraby Michèle, Piccoli Colette, Tiraby Gérard, Yamasaki Hiroshi, Mesnil Marc
Unit of Multistage Carcinogenesis, International Agency for Research on Cancer, 150 cours Albert Thomas, Lyon cedex 08, France.
Cancer Lett. 2009 Sep 8;282(1):43-7. doi: 10.1016/j.canlet.2009.02.050. Epub 2009 Apr 1.
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.
在为杀死癌细胞而精心设计的基因治疗策略中，有一种策略使用了编码胞嘧啶脱氨酶（CD）的CodA基因，该酶可将5-氟胞嘧啶（5-FC）转化为有毒的5-氟尿嘧啶（5-FU）。为了增强5-FC的代谢激活作用，我们制备了一种携带CodA和upp（尿嘧啶磷酸核糖基转移酶）基因的载体，该载体使HeLa细胞对5-FC敏感，并增强了一种非由间隙连接介导的旁观者效应。然而，如果细胞之间存在通讯，1%的CD(+)-UPP(+)细胞能够杀死40%的细胞群体。这表明，在CD(+)-UPP(+)细胞比例非常低的情况下，CodA和upp通过依赖间隙连接的机制诱导旁观者效应。
