Aspirin protects melanocytes and keratinocytes against UVB-induced DNA damage in vivo.

Abstract Ultraviolet (UV) radiation promotes skin cancer through multiple mechanisms, including induction of inflammation, oxidative stress, and DNA damage such as 8-oxoguanine (8-OG) and cyclobutane pyrimidine dimers (CPD). We investigated whether the anti-inflammatory activities of aspirin (ASA) could protect against UVB-induced DNA damage and skin carcinogenesis. ASA reduced UVB-induced 8-OG and CPD in Melan-a melanocytes and HaCat keratinocytes. Skin from UVB-irradiated C57BL/6 mice receiving 0.4 mg ASA daily by gavage exhibited less inflammation, fewer sunburn cells, and reduced 8-OG lesions than skin from irradiated control animals. ASA similarly reduced UVB-induced sunburn cells, 8-OG, and CPD lesions in skin of melanoma-prone TN61R mice, and this was associated with decreased prostaglandin (PG) E2 in plasma and skin. These effects of ASA, however, did not delay melanoma onset in TN61R mice exposed to a single neonatal dose of UVB. In SKH1-E mice prone to squamous cell carcinoma (SCC), ASA reduced plasma and skin PGE2 levels and indices of UVB-induced DNA damage, and delayed SCC onset induced by chronic UVB. These results indicate that ASA can protect against UVB-induced inflammation in skin and reduce UVB-induced DNA damage in both melanocytes and keratinocytes. These effects translated into greater chemopreventive efficacy for UVB-induced SCC than melanoma mouse models.