Modification of Multistage Skin Carcinogenesis in Mice

The multistage model of mouse skin tumorigenesis has been extremely useful for studying various factors that modify the carcinogenic process. Using this model system one can specifically study the effects of potential modifiers on both the initiation and the promotion stages independently. Studies have been performed on many exogenous compounds that have the capacity to inhibit (and in some cases enhance) the initiation phase by either: (i) alteration of the metabolism of the carcinogen (decreased activation and/or increased detoxification); (ii) scavenging of active molecular species of carcinogens to prevent their reaching critical target sites in the cells; (iii) competitive inhibition; or (iv) modulation of epidermal DNA synthesis. In addition, there have been a number of studies on compounds that either inhibit (or again in some cases enhance) promotion of skin carcinogenesis by (i) altering the state of differentiation; (ii) inhibiting the promoter-induced cellular proliferation; (iii) preventing gene activation by promoters; or (iv) scavenging free radicals and reactive oxygen species. Recent studies have also begun to unravel the nature of the tumor progression process of skin carcinogenesis. Many factors can modulate tumor progression including: (i) subsequent exposure to genotoxic agents; (ii) dose, duration and frequency of promoter treatment, (iii) chemical nature of the promoting agent. The multistage model of skin tumorigenesis has also begun to provide insight into the role of specific dietary, immunologic, and genetic factors involved in chemical carcinogenesis. It is believed that further study of all of these factors will greatly enhance our understanding of the process of chemical carcinogenesis in epithelial tissues in general as well as the process of skin carcinogenesis specifically. Finally, a greater understanding of those factors modifying skin tumorigenesis in mice will provide valuable information on the further development of early detection and prevention strategies for chemical carcinogenesis in humans.