Ultraviolet radiation accelerates NRas-mutant melanomagenesis: A cooperative effect blocked by sunscreen

Pigment Cell Melanoma Res. 2017 Sep;30(5):477-487. doi: 10.1111/pcmr.12601. Epub 2017 Jul 4.

Abstract

To mitigate melanoma risk, sunscreen use is widely advocated; yet, the ability of sunscreens to prevent melanoma remains controversial. Here, we test the tenet that sunscreens limit melanoma risk by blocking ultraviolet radiation (UV)-induced DNA damage using murine models that recapitulate the genetics and spontaneous evolution of human melanoma. We find that a single, non-erythematous dose of UV dramatically accelerates melanoma onset and increases tumor multiplicity in mice carrying an endogenous, melanocyte-specific NRas61R allele. By contrast, transient UV exposure does not alter tumor onset in mice lacking p16INK4a or harboring an NRas12D allele. To block the rapid onset of melanoma cooperatively caused by UV and NRas61R , we employed a variety of aerosol sunscreens. While all sunscreens delayed melanoma formation and blocked UV-induced DNA damage, differences in aerosol output (i.e., amount applied/cm2 ) caused variability in the cancer preventative efficacy of products with identical sunburn protection factor (SPF) ratings.

Keywords: NRAS; melanoma; mouse model; sunscreen; ultraviolet.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aerosols
  • Animals
  • Carcinogenesis / pathology*
  • Carcinogenesis / radiation effects*
  • Codon / genetics
  • DNA Damage
  • Disease-Free Survival
  • Dose-Response Relationship, Radiation
  • Melanoma / drug therapy*
  • Melanoma / pathology*
  • Mice, Inbred C57BL
  • Mutation / genetics*
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / pathology
  • Sun Protection Factor
  • Sunscreening Agents / therapeutic use*
  • Ultraviolet Rays*
  • ras Proteins / genetics*

Substances

  • Aerosols
  • Codon
  • Sunscreening Agents
  • ras Proteins