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

Pigment Cell Melanoma Res. 2013 Nov;26(6):835-44. doi: 10.1111/pcmr.12157. Epub 2013 Sep 9.

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.

Keywords: MC1R; melanocytes; melanoma; proliferation; sun exposure.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Apoptosis / drug effects
  • Apoptosis / radiation effects
  • Caspase 3 / metabolism
  • Cell Count
  • Cell Proliferation / drug effects
  • Cell Proliferation / radiation effects
  • DNA Damage
  • Erythema / pathology
  • Female
  • Fluorescent Antibody Technique
  • Genetic Variation*
  • Humans
  • Male
  • Melanocytes / drug effects*
  • Melanocytes / enzymology
  • Melanocytes / pathology
  • Melanocytes / radiation effects*
  • Melanoma / pathology*
  • Phenotype
  • Pyrimidine Dimers / metabolism
  • Receptor, Melanocortin, Type 1 / genetics*
  • Sunbathing
  • Sunscreening Agents / pharmacology*
  • Tumor Suppressor Protein p53 / metabolism
  • Ultraviolet Rays*

Substances

  • Pyrimidine Dimers
  • Receptor, Melanocortin, Type 1
  • Sunscreening Agents
  • Tumor Suppressor Protein p53
  • Caspase 3