Abstract PL06-03: Role of the circadian clock in skin cancer prevention and sunburn erythema

Abstract

Abstract Epidemiological studies of humans and experimental studies with mouse models suggest that sunburn apoptosis and erythema as a result of exposure to excessive UV light and damage to DNA confers an increased risk for melanoma and non-melanoma skin cancer. The early inflammatory response to UV exposure, sunburn, follows molecular and cellular responses including DNA repair and apoptosis. Previous reports have shown that nucleotide excision repair, the sole pathway for removing UV-induced DNA damage, as well as DNA replication, are regulated by the circadian clock in mouse skin. Furthermore, more skin carcinogenesis was observed in mice exposed to UV in the early morning, when repair activity was low, and replication activity was high, as compared to mice exposed in the late afternoon. Because sunburn and skin cancer are causally related, we investigated UV-induced sunburn apoptosis and erythema in mouse skin as a function of circadian time. Interestingly, sunburn apoptosis, inflammatory cytokine induction, and erythema were maximal following an acute early morning exposure to UV, and minimal following an afternoon exposure. We find that the circadian rhythmicity of erythemal response was correlated with greater UV-induced stabilization and activity of p53 protein in the early morning as compared to the late afternoon. These data provide the first evidence that the circadian clock plays an important role in the erythemal response. Furthermore, modulating either the circadian clock or the time of the day when exposure occurs may be effective in mitigating the risk for sunburn, skin cancer development and photo aging. Citation Format: Shobhan Gaddameedhi, Aziz Sancar. Role of the circadian clock in skin cancer prevention and sunburn erythema. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr PL06-03.