Karyotype evolution of the clonal rat liver cell line CL 52 during progression in vitro and in vivo

Liver cell line CL 52, derived from a diethylnitrosamine-treated rat at the stage of preneoplasia/early neoplasia, had an inconspicuous 2n karyotype when analyzed 6 months after in vitro propagation. Malignant progression was accompanied by cytogenetic alterations of chromosomes 1, 3, and 11. In addition, trisomy of chromosomes 4, 6, and 7 led to a significant reduction of the tumor latency period after retransplantation. During 4 years of cytogenetic observation, the once clonal 2n population showed a characteristic karyotype evolution: loss of diploidy, occurrence of polyploid sidelines, deletions followed by unbalanced rearrangements, clonal diversification, and selection of the in vitro most rapidly growing or in vivo most malignant cell type. The karyotype alterations in the four sublines of CL 52 are discussed with special reference to oncogenesis-related genes assigned to the involved rat chromosomes 1, 3, 11, 12, 4, 6, 7, 10. The observed karyotype evolution of this cell line exemplifies genetic/chromosome instability of carcinogen-induced preneoplastic/early neoplastic liver cells and provides a tool for analyzing, under controlled conditions, stage-dependent sequences of molecular genetic alterations in liver carcinogenesis.