Sequential studies of skin tumorigenesis in PGK mosaic mice: the effect of repeated exposure to a carcinogen on regressed mouse skin papillomas

Most mouse skin papillomas developing after 7,12-dimethylbenz[a]anthracene (DMBA) initiation followed by repeated 12-O-tetradecanoylphorbol-13-acetate (TPA) promotion are promoter-dependent; termination of promotion results in their regression. Previous evidence, from mapping the locations of papillomas and using the X-chromosome-linked phosphoglycerate kinase cell markers, shows that regression of promoter-dependent papillomas is permanent. Exposure to another course of TPA promotion was found not to induce regeneration in the regressed papillomas. To determine whether repeated exposure to a carcinogen causes regeneration of regressed papillomas, the effects of weekly applications of low doses of DMBA were tested. The results reported here indicate that regressed promoter-dependent papillomas do not regenerate when exposed repeatedly to DMBA. However, the treatment with DMBA induced many new tumors most of which were promoter-independent papillomas or malignant carcinomas. These findings provide further support for the conclusion that termination of promotion leads to permanent regression of most promoter-dependent mouse skin papillomas.