DNA contents and chromosomes of clonal lines of transformed rat liver epithelial cells and of cells from their derived tumors

Clonal lines of transformed rat liver epithelial cells, derived from a single population of cloned diploid rat liver epithelial (stem-like) cell line (WB-F344) by exposure in vitro to N methyl-N'-nitro-N-nitrosoguanidine (MNNG), produce hepatocellular carcinomas, hepatoblastomas and adeno carcinomas in syngeneic rats (Tsao and Grisham, Am. J. Pathol., 127, 168–181, 1987). In this study we show that these clonal lines demonstrate near-diploid (GN clones) or near-triploid (GP clones) aneuploidy and the universal occurrence of non-random chromosomal abnormalities. Marker chromo somes that involved four autosomes-a non-reciprocal translocation involving chromosomes 1 and 7 (t1q43;7q34), and addition of DNA of unknown origin to the pericentro meric regions of chromosomes 4 and 10—occurred in all of the cells of all transformed clones and in the cells of tumors that grew from them. New marker chromosomes involving the same regions of chromosomes 4 and 7 were found in several cell lines established from independent tumors. The preservation of marker chromosomes in tumor cells in the face of random loss and gain of other chromosomes suggests that these non-random aberrations were necessary for tumor formation. The presence of marker chromosomes was associated with increased expression of the c-myc gene (located at q34 on chromosome 7), the c-H-ras gene (located at q41–43 on chromosome 1) and the c-K-ras and TGFα genes (both located at unknown sites on chromosome 4), which we have previously shown to be highly correlated with tumorigenicity in these same transformed donal lines (Lee et al., Cancer Res., 51, 5238–5244, 1992).