Cytogenetic instability with balanced chromosome changes in an SV40 transformed human uroepithelial cell line

Cytogenetic analysis at the 15th, 34th, 50th, and 56th passages of an SV40 immortalized human uroepithelial cell line (SV-HUC-1) showed continuous chromosome change and marker formation. Throughout these passages the transformed cells maintained their epithelial morphology, were SV40 T antigen positive, did not shed infectious SV40 virus, and were repeatedly found to be nontumorigenic when innoculated into athymic nude mice. Each of the passages studied was characterized by extensive karyotypic changes due to formation, rearrangement, and disappearance of different markers. A marker involving chromosome 1 was stable at three of the passages studied, whereas markers involving the X chromosome changed at each passage studied. Because of the incorporation of several chromosomes or chromosome arms into markers, the karyotype was genetically balanced in the first passage studied, with no net loss or gain of chromosomal material despite a modal number of 44. In subsequent passages, despite continued instability and generation of new markers, there was a slight but additive loss of genomic balance which increased with time in culture. Since continued karyotypic rearrangements did not lead to tumorigenic conversion, it is probable that genetic instability coupled with selection for the most balanced genome may be important for the immortalization of this cell line.