In vivo studies have shown that the SENCAR mouse is unusually sensitive to skin carcinogenesis by initiation and promotion while the Balb/c mouse is resistant. We have developed a technique of grafting epidermal and dermal cells to athymic nude mice in order to form a reconstituted skin. Cell line 308RB was previously developed in this laboratory by initiation of adult Balb/c mouse skin in vivo with 7, 12-dimethylbenz[a]anthracene (DMBA), culture of the epidermal cells, and selection for cells resistant to Ca2+-induced terminal differentiation, a property of initiated cells. Using the grafting technique, we have shown that line 308RB forms benign squamous papillomas, confirming that it is an initiated, nonmalignant cell line. We have also developed cell lines from papillomas produced on both SENCAR (SP lines) and Balb/c (BP lines) mice in vivo by initiation with DMBA and promotion with 12-0-tetradecanoylphorbol-13-acetate (TPA). When grafted to nude mice, these lines produce papillomas similar to those formed by line 308RB. Line SP-1, the most extensively studied to date, produces papillomas whose size increases as the number of cells grafted increases from 16,000 to 1,600,000. Addition of normal primary epidermal cells at the time of grafting suppresses papilloma formation by SP-1 cells in proportion to the number of normal cells added. The development of these cell lines provides a means for controlled study of the suppression of Balb/c and SENCAR papilloma development by homologous and heterologous normal primary epidermal cells and the overcoming of this suppression in response to tumor promotion. Furthermore, these cell lines are a useful model for study of the conversion of benign to malignant tumor cells.
