Melanin mediated apoptosis of epidermal cells damaged by ultraviolet radiation: factors influencing the incidence of skin cancer.
Ultraviolet (UV)-induced skin cancers, including melanomas and basal/squamous cell carcinomas, occur more frequently in individuals with fair skin than in those with dark skin. Melanin plays an important role in protecting the skin against UV radiation and levels of melanin correlate inversely with amounts of DNA damage induced by UV in human skin of different racial/ethnic groups. The objectives of this study are to review recent progress in our understanding of mechanisms underlying differences in cancer incidence in skins of different colors, particularly between Black and White skin. More specifically, we review DNA damage and apoptosis in various types of skin before and after exposure to UV in our human study protocols using a single UV dose, either one minimal erythema dose (MED) or a similar low dose of 180-200 J/m2. Our data and other published reports indicate that several major mechanisms underlie the increased rates of 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. Second, rates of repair of DNA damage can differ significantly in individuals. Third, UV-induced apoptosis to remove potentially precancerous cells is significantly greater in darker skin. These results suggest that pigmented epidermis is an efficient UV filter and that UV damaged cells are removed more efficiently in darker skin. 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
Yuji
Y
Pigment Cell Research Section, Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. yujin@med.nagoya-cu.ac.jp
Beer
Janusz Z
JZ
Hearing
Vincent J
VJ
D017209:Apoptosis; D004249:DNA Damage; D004817:Epidermis / Q000528:radiation effects*; D006801:Humans; D015994:Incidence; D008543:Melanins / Q000502:physiology*; D009381:Neoplasms, Radiation-Induced / Q000453:epidemiology*; D044102:Receptor, Melanocortin, Type 1 / Q000502:physiology; D012878:Skin Neoplasms / Q000453:epidemiology*; D014466:Ultraviolet Rays / Q000009:adverse effects*
D008543:Melanins; D044102:Receptor, Melanocortin, Type 1