Properties of carcinogen altered mouse epidermal cells resistant to calcium-induced terminal differentiation

Publisher Website
Google Scholar
Abstract
Eight cell lines [X1, A1, B, X4, F, G, C, D] exhibiting resistance to Ca2+-induced terminal differentiation were derived from primary mouse epidermal cultures and their properties analyzed. The lines developed either spontaneously (2 lines) or after exposure of primary cultures to carcinogens [N-methyl-N''-nitro-N-nitrosoguanidine or 7,12-dimethylbenz[a]anthracene] or carcinogens and tumor promoter [12-O-tetradecanoyl-phorbol-13-acetate]. All but 1 of the lines were of epithelial or epithelioid morphology but 3 of the 8 lines lacked desmosomes, keratin filaments and immunoprecipitable keratin proteins, and thus could not be defined as keratinocytes. Two of the 5 keratinocyte lines were tumorigenic in syngeneic Balb/c newborns after 4 mo. in medium containing 1.2 mM Ca2+, and 3 lines remained non-tumorigenic even after 11 mo. in 1.2 mM Ca2+. All 3 of the non-keratinizing lines were tumorigenic. Tumorigenic potential of the 5 keratinocyte lines did not correlate with ploidy (as determined by DNA content), transglutaminase activity or growth in soft agar. The 2 tumorigenic keratinocyte lines contained cells which stained intensely red for .gamma.-glutamyl transpeptidase activity, while the non-tumorigenic keratinocyte lines did not. Only those lines lacking desmosomes and keratin filaments grew in soft agar, but these lines were negative for .gamma.-glutamyl transpeptidase activity. Ploidy and transglutaminase activity did not correlate with tumorigenicity in these non-keratinizing lines. Cell lines derived from cultured mouse epidermal cells and selected on the basis of their resistance to Ca2+ induced terminal differentiation may be preneoplastic. The association of additional markers with malignant change in these cell lines depended on whether or not the cells were keratinizing.