Establishment and Characterization of Cell Cultures from Methapyrileneinduced Liver Tumors in Rats

Abstract

The antihistaminic methapyrilene (MP), which is neither mutagenic in bacterial test systems nor clastogenic in mammalian cells, has been shown by Lijinsky et al. (29) to be a potent hepatocarcinogen in rats. Two cell cultures from primary hepatocellular carcinomas induced by MP were established and characterized for growth, morphology, and physiological characteristics in vitro as compared to tumor cell lines induced by known genotoxic agents. The parameters studied included: growth kinetics, colony formation in semisolid medium, tumorigenesis, karyology, y-glutamyl transpeptidase activity, membrane permeability as measured by 2-deoxyglucose uptake, and growth regulation exerted by an hepatic proliferation inhibitor (HPI). The MP-tumor derived cell cultures resembled tumor cell lines only in their resistance to growth inhibition by HPI. With all other transformation markers the tumor cell cultures resembled normal liver epithelial cells. These results are discussed in view of proposals by Potter (48) and their possible relevance to carcinogenesis.