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 a t the stage of preneoplasia/early neoplasia, had an inconspicuous 2n k aryotype 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 retransplanta tion. During 4 years of cytogenetic observation, the once clonal 2n po pulation 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 karyotyp e alterations in the four sublines of CL 52 are discussed with special reference to oncogenesis-related genes assigned to the involved rat c hromosomes 1, 3, 11, 22, 4, 6, 7, 10. The observed karyotype evolution of this cell line exemplifies genetic/chromosome instability of carci nogen-induced preneoplastic/early neoplastic liver cells and provides a tool for analyzing, under controlled conditions, stage-dependent seq uences of molecular genetic alterations in liver carcinogenesis.