Trabanelli C, Corallini A, Gruppioni R, Sensi A, Bonfatti A, Campioni D, Merlin M, Calza N, Possati L, Barbanti-Brodano G
Department of Experimental and Diagnostic Medicine, University of Ferrara, Italy.
Virology. 1998 Apr 10;243(2):492-6. doi: 10.1006/viro.1998.9080.
Human fibroblasts, transfected with a recombinant DNA containing the neo gene and BK virus (BKV) early region, which expresses BPV large T antigen (TAg), show cytogenetic alterations characterized by dicentric chromosomes and other structural aberrations such as deletions, duplications, translocations, and ring chromosomes. Such alterations were absent or significantly less frequent in human fibroblasts transfected with a plasmid expressing only the neo gene. The chromosome damage in BKV-transfected cells was evident before the appearance of the morphologically transformed phenotype and therefore seems to be a primary effect of TAg expression in human cells. The specific pattern of chromosome aberrations suggests the prevalence of an indirect clastogenic effect, determined by the inhibition of p53 regulatory functions on genome stability by BKV TAg. Due to the widespread distribution of BKV in the human population and to the latent state of BKV DNA in many human organs, the clastogenic activity of BKV TAg may potentially participate in an oncogenic process involving BKV latently infected cells.
用人成纤维细胞转染含有新霉素基因(neo基因)和BK病毒(BKV)早期区域的重组DNA,该区域表达牛乳头瘤病毒大T抗原(TAg),结果显示细胞遗传学改变,其特征为双着丝粒染色体以及其他结构畸变,如缺失、重复、易位和环状染色体。在用仅表达neo基因的质粒转染的人成纤维细胞中,此类改变不存在或明显较少见。在形态学转化表型出现之前,BKV转染细胞中的染色体损伤就很明显,因此似乎是TAg在人细胞中表达的主要效应。染色体畸变的特定模式表明间接致断裂效应普遍存在,这是由BKV TAg对p53调控基因组稳定性功能的抑制所决定的。由于BKV在人群中广泛分布,且BKV DNA在许多人体器官中处于潜伏状态,BKV TAg的致断裂活性可能潜在地参与涉及BKV潜伏感染细胞的致癌过程。