Antioxidants and multistage carcinogenesis in mouse skin.

The two-step initiation-promotion protocol for the induction of skin tumors in mice is a convenient model to elucidate what molecular events are involved in the multistage process of carcinogenesis and how they can be modulated. The current theories concerning the mechanisms of skin tumor initiation, stages 1 and 2 of tumor promotion, and tumor progression are reviewed. Because chemical carcinogens and tumor promoters may, directly or indirectly, generate reactive oxygen species (ROS) and because various antioxidants inhibit effectively some of the biochemical and biological events linked to tumor initiation, promotion and/or progression, it is conceivable that different sequences and levels of free radical-induced macromolecule damage may contribute to the evolution of the epidermal target cells from the preneoplastic stage to the malignant stage.