Modification of some biological properties of HeLa cells containing adeno-associated virus DNA integrated into chromosome 17
Modification of some biological properties of HeLa cells containing adeno-associated virus DNA integrated into chromosome 17
复制标题
含有整合至 17 号染色体的腺相关病毒 DNA 的 HeLa 细胞某些生物学特性的改变
作者：
C. Walz;J. Schlehofer
已知细小病毒干扰细胞转化和致癌作用。由于感染腺相关病毒（AAV）经常将其DNA整合到细胞基因组中，我们分析了这种整合是否会影响人肿瘤细胞系HeLa的转化表型。具有整合的AAV DNA的三个独立HeLa细胞克隆的分析（HA-3x、HA-16和HA-28）显示这些细胞的以下表型变化：（i）生长速率降低，（ii）血清需求增加，（iii）软琼脂中菌落形成能力降低，（iv）塑料上克隆效率降低，（v）对遗传毒性剂的敏感性升高（N-甲基-N '-硝基-N-亚硝基胍、7，12-二甲基苯并[a]蒽、人肿瘤坏死因子α、UV照射[256 nm]和加热[42 ℃]），和（vi）对细小病毒H-1的细胞溶解作用的敏感性降低。当将来自含有AAV DNA的HeLa细胞的肿瘤移植到裸鼠中时，也在体内观察到生长速率降低和对γ射线的敏感性增强。HeLa细胞生物学特性的这种改变与整合的AAV基因组的数量、整合的AAV DNA的物理结构和AAV基因的转录无关。在分析的三个HeLa细胞克隆中，发现AAV DNA的整合优先发生在17号染色体的长臂上。这些发现表明，腺相关病毒DNA的基因组整合可以改变人类肿瘤细胞的生物学特性。
Parvoviruses are known to interfere with cellular transformation and carcinogenesis. Since infecting adeno-associated virus (AAV) frequently integrates its DNA into the cellular genome, we analyzed whether this integration influences the transformed phenotype of the human tumor cell line HeLa. Analysis of three independent HeLa cell clones with integrated AAV DNA (HA-3x, HA-16, and HA-28) revealed the following phenotypic changes of these cells: (i) reduced growth rate, (ii) increased serum requirement, (iii) reduced capacity for colony formation in soft agar, (iv) reduced cloning efficiency on plastic, (v) elevated sensitivity to genotoxic agents (N-methyl-N'-nitro-N-nitrosoguanidine, 7,12-dimethylbenz[a]anthracene, human tumor necrosis factor alpha, UV irradiation [256 nm], and heat [42 degrees C]), and (vi) reduced sensitivity to the cytolytic effect of parvovirus H-1. Reduced growth rate and enhanced sensitivity to gamma irradiation were also observed in vivo when tumors from AAV DNA-containing HeLa cells were transplanted into nude mice. This alteration of the biological properties of HeLa cells was independent of the number of AAV genomes integrated, the physical structure of integrated AAV DNA, and the transcription of AAV genes. Integration of AAV DNA was found to occur preferentially on the long arm of chromosome 17 in the three HeLa cell clones analyzed. These findings demonstrate that genomic integration of AAV DNA can alter the biological properties of human tumor cells.
腺相关病毒 2 号基因组在永生和永生人类细胞中的拯救和复制。
影响因子：
4.6
作者：
Nahreini,P;Srivastava,A
通讯作者：
Srivastava,A
DOI：
10.1073/pnas.85.23.9138
发表时间：
1988-12-01
影响因子：
11.1
作者：
PINKEL, D;LANDEGENT, J;GRAY, J
通讯作者：
GRAY, J