12-0-Tetradecanoylphorbol-13-acetate-induced amplification of mesenchymal tumorigenesis in the mouse skin.

Skin tumors were induced in 6-week-old female Swiss albino mice by a single subcutaneous (SC) injection of 20-methylcholanthrene (MCA) in the right scapular region and the animals were then divided into four groups. Mice in group I did not receive further treatment. Six weeks after MCA injection, those in groups II and III received twice weekly applications of 0.1 ml acetone and 1.8 nmol 12-0-tetradecanoylphorbol-13-acetate (TPA) in 0.1 ml acetone, respectively, at the site of MCA injection until tumor development. Group IV animals were divided into four subsets and administered two, four, six, or eight TPA applications commencing 6 weeks after carcinogen injection. The effect of TPA pretreatment on MCA-induced tumorigenesis was studied in animals in group V. In mice treated with MCA alone, the most predominant mesenchymal tumor type is fibrosarcoma with induction of some rhabdomyosarcomas. Mixed mesenchymal tumors consisting of fibrosarcoma, rhabdomyosarcoma, or hibernoma were observed in only 12% of the animals. The number of animals bearing mixed mesenchymal tumors such as fibrosarcoma, rhabdomyosarcoma, hibernoma, and/or liposarcoma increased to 46% in mice receiving MCA + TPA until tumor development. Interestingly, liposarcomas were not found at all in animals treated with MCA alone. The data indicates that TPA application to precancerous mouse skin enhances mesenchymal tumorigenesis.