Transfection of a vector expressing wild-type p53 into cells of two human glioma cell lines enhances radiation toxicity
Transfection of a vector expressing wild-type p53 into cells of two human glioma cell lines enhances radiation toxicity
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DOI：
10.2307/3579642
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发表时间：
1998-07-01
影响因子：
3.4
通讯作者：
Vaughan, ATM
中科院分区：
文献类型：
--
作者：
Geng, L;Walter, S;Vaughan, ATM
将含有野生型p53或β-Gal标记基因的复制缺陷型腺病毒(Adv5)载体分别导入人胶质瘤细胞系T98G(突变体)和U87 MG(野生型)细胞。流式细胞仪和Western blotting显示野生型P53基因在各细胞系中均有成功表达。与对照细胞或含有β-半乳糖载体的细胞相比，P53表达载体的存在在两种细胞系中都是有毒的。在可检测到毒性的Adv5P53载体水平上，辐射效果增强，细胞杀伤率增加一倍。在T98G细胞中，P53载体的存在导致照射后发生凋亡的细胞数量增加，而在U87 MG细胞中观察到较小的且仅有相加反应。反之，照射后的Adv5P53阳性的U87 MG细胞微核形成增加，表明有丝分裂活性破坏，而T98G细胞则没有。这些数据表明，P53表达载体有效地增强了这些人脑胶质瘤细胞系的辐射杀伤力，但其作用机制不能简单地与激活P53依赖的凋亡途径有关。(C)1998年，由辐射研究学会提供。
Replication-deficient adenovirus (Adv5)-based vectors containing either wild-type p53 or the beta-gal marker gene were introduced into cells of the T98G (p53 mutant) and U87MG (p53 wild-type) human glioma cell lines. The wild-type p53 gene was successfully expressed in each cell line as shown by flow cytometry and Western blotting. The presence of the p53-expressing vector was toxic in both cell lines compared to control cells or to those containing the beta-gal vector. At levels of Adv5p53 vector that produced detectable toxicity, the effect of irradiation was enhanced, producing a twofold increase in cell killing. In the T98G cells, the presence of the p53 vector resulted in an increase in the number of cells undergoing apoptosis after irradiation, whereas a smaller and only additive response was observed in the U87MG cells. Conversely, an increase in micronucleus formation, indicating corrupt mitotic activity, was observed in irradiated Adv5p53-positive U87MG cells but not in T98G cells. These data suggest that p53-expressing vectors effectively enhance radiation lethality in these human glioma cell lines, but that the mechanism of action cannot be simply related to activation of the p53-dependent pathway to apoptosis. (C) 1998 by Radiation Research Society.