Production of epithelial and mesenchymal tumours with rat liver cells transformed in vitro

Epithelial‐like cells originating from the livers of 10‐day and 8‐week‐old BD rats were established in culture. The cells were treated in vitro for 1 or 4 weeks with dimethyl‐nitrosamine (DMN) or N‐methyl‐N′‐nitro‐N‐nitrosoguanidine (MNNG). Although some structural changes were observed in treated cells, it was not possible to score for morphological transformation in vitro. Newborn syngeneic rats were injected with 1.5‐2 × 106 treated or 1.5‐5 × 106 control cells at various times up to 38 weeks from the beginning of treatment with the carcinogen. Following the injection of DMN‐treated cells, a total of 32 of the 42 injected rats developed tumours, of which 17 were epithelial, 10 carcinosarcomas and 5 fibrosarcomas. Following the injection of the MNNG‐treated cells into 61 rats, a total of 30 tumours were observed, including 8 carcinomas, 9 carcinosarcomas and 13 fibroscarcomas. Tumours, mainly of the mesenchymal type, were also observed in rats inoculated with control cells but at a lower frequency. The observation of mesenchymal tumours is attributed to the presence of a mixed population of epithelial and mesenchymal cells in the original culture.