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

Overview

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 NRas^61R allele. By contrast, transient UV exposure does not alter tumor onset in mice lacking p16^INK^4a or harboring an NRas^12D allele. To block the rapid onset of melanoma cooperatively caused by UV and NRas^61R , 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.