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HUMAN SKIN RESPONSES TO UV RADIATION: PIGMENT IN THE UPPER EPIDERMIS PROTECTS AGAINST DNA DAMAGE IN THE LOWER EPIDERMIS AND FACILITATES APOPTOSIS.

Yamaguchi1, Y., Takahashi1, K., Zmudzka2, B.Z., Kornhauser3, A., Miller2, S.A., Tadokoro1, T., Berens1, W., Beer2, J.Z., and Hearing1, V.J. 1Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA; 2Center for Devices and Radiological Health, Food and Drug Administration, Rockville, Maryland, USA; and 3Center for Food Safety and Applied Nutrition, U. S. Food and Drug Administration, College Park, Maryland, USA.
Abstract

This study by researchers at the National Cancer Institute and the US Food and Drug Administration demonstrated how MatTek’s MelanoDerm reconstructed 3-D in vitro human skin tissues containing both keratinocytes and melanocytes could be used to investigate how increased melanin concentrations in human skin can act as a UV radiation “filter”, a phenomenon first seen in studies involving the UV irradiation of the skin of 92 human volunteers. 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. Researchers at the National Cancer Institute and the US Food and Drug Administration 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. These researchers 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.

Keywords

DNA damage, MEL-300-A, MEL-300-B, MEL-300-C, Melanin, MelanoDerm, TUNEL staining, UV Radiation

Materials Tested

UVB-irradiated

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