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Melanin mediated apoptosis of epidermal cells damaged by ultraviolet radiation: factors influencing the incidence of skin cancer

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Abstract

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.

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Abbreviations

6,4PP:

(6-4) Photoproducts

CPD:

Cyclobutane pyrimidine dimers

MC1R:

Melanocortin 1 receptor

MED:

Minimal erythema dose

MITF:

Microphthalmia transcription factor

PAR-2:

Protease activated receptor-2

PI:

Propidium iodide

TUNEL:

TdT-mediated dUTP nick end labeling

UV:

Ultraviolet

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Acknowledgments

This work was supported in part by the Lydia O’Leary Memorial Foundation, by a SHISEIDO Grant for Science Research, by the Rhoto award, by a grant-in-aid from the Ministry of Education, Culture, Sports, Science and Technology (Japan), by the FDA Office of Science and Center for Devices and Radiological Health, and by the Intramural Research Program of the NIH, National Cancer Institute. The authors are grateful to Drs. Taketsugu Tadokoro, Kaoruko Takahashi, Sharon A. Miller, Barbara Z. Zmudzka and Sergio G. Coelho for their helpful discussions of this work.

Conflict of interest statement

None of the authors has any potential conflict of interest.

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Authors and Affiliations

  1. Pigment Cell Research Section, Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    Yuji Yamaguchi & Vincent J. Hearing

  2. Department of Dermatology, Osaka University Graduate School of Medicine, Suita-shi, Osaka, Japan

    Yuji Yamaguchi

  3. Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, Nagoya-shi, Aichi, Japan

    Yuji Yamaguchi

  4. Center for Devices and Radiological Health, Food and Drug Administration, Rockville, MD, USA

    Janusz Z. Beer

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  1. Yuji Yamaguchi
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Correspondence to Yuji Yamaguchi.

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Yamaguchi, Y., Beer, J.Z. & Hearing, V.J. Melanin mediated apoptosis of epidermal cells damaged by ultraviolet radiation: factors influencing the incidence of skin cancer. Arch Dermatol Res 300 (Suppl 1), 43–50 (2008). https://doi.org/10.1007/s00403-007-0807-0

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