title: The effect of MC1R variants and sunscreen on the response of human melanocytes in vivo to ultraviolet radiation and implications for melanoma.
abstract: 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.
authors: Centre for Research Excellence in Sun and Health, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Qld, Australia; Genetics & Population Health Division, QIMR Berghofer Medical Research Institute, Brisbane, Qld, Australia.
authors: Elke
authors: E
authors: Hacker
authors: Zachary
authors: Z
authors: Boyce
authors: Michael G
authors: MG
authors: Kimlin
authors: Leesa
authors: L
authors: Wockner
authors: Thomas
authors: T
authors: Pollak
authors: Sam A
authors: SA
authors: Vaartjes
authors: Nicholas K
authors: NK
authors: Hayward
authors: David C
authors: DC
authors: Whiteman
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D053148:Caspase 3 / Q000378:metabolism; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D004249:DNA Damage; D004890:Erythema / Q000473:pathology; D005260:Female; D005455:Fluorescent Antibody Technique; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008544:Melanocytes / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology / Q000528:radiation effects*; D008545:Melanoma / Q000473:pathology*; D010641:Phenotype; D011740:Pyrimidine Dimers / Q000378:metabolism; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics*; D055108:Sunbathing; D013473:Sunscreening Agents / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014466:Ultraviolet Rays
chemical_list: D011740:Pyrimidine Dimers; D044102:Receptor, Melanocortin, Type 1; D013473:Sunscreening Agents; D016159:Tumor Suppressor Protein p53; D053148:Caspase 3
keywords: MC1R; melanocytes; melanoma; proliferation; sun exposure