Adenoviral vector cytotoxicity depends in part on the transgene encoded.
Adenoviral vector cytotoxicity depends in part on the transgene encoded.
复制标题
腺病毒载体的细胞毒性部分取决于所编码的转基因。
DOI：
10.1006/bbrc.2000.3213
复制
发表时间：
2000
影响因子：
3.1
通讯作者：
Baum,BJ
中科院分区：
文献类型：
--
作者：
Zheng,C;Goldsmith,CM;O'Connell,BC;Baum,BJ
第一代腺病毒载体在体外诱导G2/M期停滞和细胞死亡(m.o.i‘S)。目前尚不清楚这种细胞毒性是否完全与腺病毒基因有关，或者部分受到编码的转基因的影响。我们用7个相对较低(50)或更高(200m.I.)的载体在上皮细胞中研究了这个问题。这些载体不包含转基因(±启动子)、编码细胞质报告蛋白的转基因(两个荧光素酶结构；β-半乳糖苷酶)或编码分泌蛋白的转基因(α1-抗胰蛋白酶；生长激素)。在24小时后，有一名嫌犯。在50个载体中，编码胞质报告蛋白的载体具有最大的细胞毒性(∼为35-40%的G2/M期细胞)。不含转基因载体的G2/M细胞具有较低的细胞毒作用(∼为15%、负23%或23%加启动子)。编码分泌蛋白的载体使∼22-25%的细胞处于G2/M期，当测量细胞数时，也出现类似的模式。结果与转基因产物的稳态水平无关。在较高的m.o.i时，所有的载体都导致了显著的生长迟缓。这是首次证明腺病毒载体诱导的细胞毒作用部分与编码的转基因有关。
First-generation adenoviral vectors induce G2/M arrest and cell death at high multiplicities of infection (m.o.i.'s) in vitro. It is unclear whether this cytotoxicity is entirely adenoviral gene related or influenced in part by the encoded transgene. We examined this question in epithelial cells using seven vectors at relatively low (50) or higher (200) m.o.i.'s. The vectors contained no transgene (±promoter), transgenes encoding a cytoplasmic reporter protein (two luciferase constructs; β-galactosidase), or transgenes encoding a secretory protein (α1-antitrypsin; growth hormone). After 24 h with a m.o.i. of 50, vectors encoding cytoplasmic reporter proteins led to greatest cytotoxicity (∼35–40% cells in G2/M). Vectors without a transgene resulted in lower cytotoxicity (∼15%, minus, or 23%, plus promoter, cells in G2/M). Vectors encoding secretory proteins led to ∼22–25% cells in G2/M. A similar pattern resulted when cell number was measured. Results were unrelated to the steady-state levels of transgene product. At the higher m.o.i., all vectors caused substantial growth retardation. This is the first demonstration that adenoviral vector-induced cytotoxic effects are in part related to the transgene encoded.