Human skin responses to UV radiation: pigment in the upper epidermis protects against DNA damage in the lower epidermis and facilitates apoptosis

ABSTRACT Melanin plays an important role in protecting the skin against UV radiation, and melanomas and basal/squamous cell carcinomas occur more frequently in individuals with fair/light skin. We previously reported that levels of melanin correlate inversely with amounts of DNA damage induced by UV in normal human skin of different racial/ethnic groups. We have now separately examined DNA damage in the upper and lower epidermal layers in various types of skin before and after exposure to UV and have measured subsequent apoptosis and phosphorylation of p53. The results show that two major mechanisms underlie the increased photocarcinogenesis in fair/light skin. First, UV‐induced DNA damage in the lower epidermis (including keratinocyte stem cells and melanocytes) is more effectively prevented in darker skin, suggesting that the pigmented epidermis is an efficient UV filter. Second, UV‐induced apoptosis is significantly greater in darker skin, which suggests that UV‐damaged cells may be removed more efficiently in pigmented epidermis. The combination of decreased DNA damage and more efficient removal of UV‐damaged cells may play a critical role in the decreased photocarcinogenesis seen in individuals with darker skin.—Yamaguchi, Y., Takahashi, K., Zmudzka, B. Z., Kornhauser, A., Miller, S. A., Tadokoro, T., Berens, W., Beer, J. Z., Hearing, V. J. Human skin responses to UV radiation: pigment in the upper epidermis protects against DNA damage in the lower epidermis and facilitates apoptosis. FASEB J. 20, E630–E639 (2006)