Phenotypic expression in spontaneously transformed cultured rat liver epithelial cells

Five clonal cell strains of an early-passage normal rat liver epithelial cell line were transformed spontaneously using the protocol of "selective culture" condition. Twelve cell lines were established from the tumors produced after injecting these transformed cells into 1-day-old syngeneic rats. The phenotypic expressions of these spontaneously transformed tumor cell lines were studied and compared to those of cell lines obtained from tumors produced by rat liver epithelial cells transformed by N-methyl-N'-nitro-N-nitrosoguanidine. Like the chemically induced tumor cells, spontaneously transformed tumor cells exhibited phenotypic heterogeneity in the expression of isoenzymes, proto-oncogenes, growth factors and their receptors, and cellular responses to the effect of growth factors. However, unlike the chemically induced tumor cells, these spontaneously induced tumor cells did not express the "resistant phenotypes" characteristic of chemically induced or promoted tumors. Although all the spontaneously induced tumor cell lines expressed variable amounts of transforming growth factor-alpha mRNA, it was not functionally coordinated with the expression of its receptor, the epidermal growth factor receptor. Thus, spontaneously transformed rat liver epithelial cells demonstrate both similarity and diversity in their phenotypic expression when compared to their chemically induced counterpart. This model of spontaneous transformation of cultured rat liver epithelial cells may be useful for the mechanistic study of non-chemically induced carcinogenesis.