Sequential studies of skin tumorigenesis in phosphoglycerate kinase mosaic mice: effect of resumption of promotion on regressed papillomas.

Most mouse skin papillomas induced by 7,12-dimethylbenz(a)-anthracene initiation followed by 12-O-tetradecanoylphorbol-13 acetate (TPA) promotion are benign promoter-dependent papillomas which regress after cessation of promotion, but some benign tumors (promoter-independent papillomas) do not regress, and a few carcinomas seem to develop from progressive growth of these tumors. We have tested whether a second course of TPA promotion induces regeneration in regressed promoter-dependent papillomas and advances them to malignancy. The regression and regeneration of these papillomas were determined by serial photographs, measurements of coordinates, histopathological evaluation, and X-chromosome-linked phosphoglycerate kinase enzyme cellular markers. Most of the regressed promoter-dependent papillomas did not regenerate. However, the second course of TPA promotion induced rapid development of many new papillomas, some of which advanced to promoter-independent papillomas and a carcinoma. This finding suggests that there are more abnormal cells in the initiated mouse skin than those detected with a single course of TPA promotion.