ABSTRACT
This chapter reviews work on the mechanisms of skin carcinogenesis, with a particular emphasis on the roles of oxidants. It discusses the roles of endogenous antioxidant defenses in preventing oxidative damage in the skin and the pharmacology of antioxidants in skin cancer prevention. The skin is uniquely challenged by oxidants due to its role as a barrier. It is exposed to high oxygen tensions, which increase its vulnerability to oxidative damage. The human skin contains a variety of enzymatic and non-enzymatic antioxidant defenses. Thiol containing molecules include glutathione and thioredoxin. Irradiation of mice led to the depletion of many of these antioxidants in the epidermis, reflecting either their activity in free radical scavenging or their destruction by ultraviolet light (UV). A large body of evidence indicates that UV-induced skin cancer involves multiple consequences of UV photochemistry. Evidence for multiple anticancer mechanisms comes from both in vitro and in vivo studies and underscores the multiple roles of antioxidants.
