CHROMOSOMAL-ABERRATIONS INDUCED BY BK VIRUS T-ANTIGEN IN HUMAN FIBROBLASTS

Human fibroblasts, transfected with a recombinant DNA containing the n eo gene and BK Virus (BKV) early region, which expresses BKV large T a ntigen (TAg), show cytogenetic alterations characterized by dicentric chromosomes and other structural aberrations such as deletions, duplic ations, translocations, and ring chromosomes. Such alterations were ab sent or significantly less frequent in human fibroblasts transfected w ith a plasmid expressing only the neo gene. The chromosome damage in B KV-transfected cells was evident before the appearance of the morpholo gically transformed phenotype and therefore seems to be a primary effe ct of TAg expression in human cells. The specific pattern of chromosom e aberrations suggests the prevalence of an indirect clastogenic effec t, 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 org ans, the clastogenic activity of BKV TAg may potentially participate i n an oncogenic process involving BKV latently infected cells. (C) 1998 Academic Press.