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

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 MC 1R 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 MC 1R variants (97% increase) was significantly less than those with wild‐type MC 1R (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.