The effect of MC1R variants and sunscreen on the response of human melanocytes in vivo to ultraviolet radiation and implications for melanoma

Authors

  • Elke Hacker,

    1. Centre for Research Excellence in Sun and Health, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Qld, Australia
    2. Genetics & Population Health Division, QIMR Berghofer Medical Research Institute, Brisbane, Qld, Australia
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  • Zachary Boyce,

    1. Centre for Research Excellence in Sun and Health, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Qld, Australia
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  • Michael G. Kimlin,

    1. Centre for Research Excellence in Sun and Health, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Qld, Australia
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  • Leesa Wockner,

    1. Statistics Unit, QIMR Berghofer Medical Research Institute, Brisbane, Qld, Australia
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  • Thomas Pollak,

    1. Genetics & Population Health Division, QIMR Berghofer Medical Research Institute, Brisbane, Qld, Australia
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  • Sam A. Vaartjes,

    1. Centre for Research Excellence in Sun and Health, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Qld, Australia
    2. Genetics & Population Health Division, QIMR Berghofer Medical Research Institute, Brisbane, Qld, Australia
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  • Nicholas K. Hayward,

    1. Genetics & Population Health Division, QIMR Berghofer Medical Research Institute, Brisbane, Qld, Australia
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  • David C. Whiteman

    Corresponding author
    1. Centre for Research Excellence in Sun and Health, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Qld, Australia
    2. Genetics & Population Health Division, QIMR Berghofer Medical Research Institute, Brisbane, Qld, Australia
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Summary

We conducted a clinical trial to compare the molecular and cellular responses of human melanocytes and keratinocytes in vivo to solar-simulated ultraviolet radiation (SSUVR) in 57 Caucasian participants grouped according to MC1R genotype. We found that, on average, the density of epidermal melanocytes 14 days after exposure to 2 minimal erythemal dose (MED) SSUVR was twofold higher than baseline (unirradiated) skin. However, the change in epidermal melanocyte counts among people carrying germline MC1R variants (97% increase) was significantly less than those with wild-type MC1R (164% increase; P = 0.01). We also found that sunscreen applied to the skin before exposure to 2 MED SSUVR completely blocked the effects of DNA damage, p53 induction, and cellular proliferation in both melanocytes and keratinocytes.

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