ESTABLISHMENT AND CHARACTERIZATION OF A NONTUMORIGENIC CELL-LINE DERIVED FROM A HUMAN HEPATOCELLULAR ADENOMA EXPRESSING HEPATOCYTE-SPECIFICMARKERS

In the present study the establishment and characterization of a nontu morigenic Liver epithelial cell line (HACL-1) derived from a human hep atocellular adenoma is described. The HACL-1 cells have a finite life span (i.e., they proliferate for a period of 2 months and then senesce ), show cell-cell contact inhibition, do not grow in soft agar, are no t tumorigenic when injected in nude mice, and possess a normal diploid karyotype. The cultured cells resemble hepatocytes, but exhibit some features of dedifferentiation. At the ultrastructural level the cells are endowed with round or oval nuclei, abundant cytoplasmic organelles , and varying amounts of glycogen. The rough endoplasmic reticulum is disorganized, while peroxisomes and matrix granules within mitochondri a are lacking. HACL-1 cells are cytokeratin 18-positive as well as (tr ansiently) albumin- and alpha-fetoprotein-positive, but do not express cytokeratin 19. Furthermore, no mutations were observed in exons 5-8 of the tumor suppressor gene p53. Taken together these results show th at HACL-1 cells are nontumorigenic proliferating liver epithelial cell s, which might prove to be of great value in future studies on diverse aspects of human liver cell biology and carcinogenesis. (C) 1997 Acad emic Press.