DNA damage and repair in human skin: Pathways and questions

Skin, the principal barrier between human internal organs and the external environment, is assaulted daily with physical and chemical carcinogens, promoters, and modifiers of biological responses to such agents. DNA is the principal target for most carcinogens, and DNA in skin is particularly at risk. It is subject to damage not only from ingested compounds and their metabolic products, but also from externally applied or encountered chemicals, as well as from physical carcinogens such as sunlight and cosmetic or medical sources of ultraviolet radiation. Three major factors determine the balance between damage to DNA of skin and the biological consequences of that damage: (1) the frequencies and types of lesions, (2) the ability of the individual to repair a lesion, and (3) the strategy that skin employs to deal with the different spectra of lesions inflicted under varying environmental conditions. Thus, cellular responses to DNA damage, including repair of DNA lesions, are critical factors in determining the final level of damage and its consequences.