Abstract 2258: Tempol diet provides chemoprotection against UV-induced skin cancer in mice with epidermal Smad4 deletion

Abstract

Abstract Solar ultraviolet (UV) radiation is the primary cause of skin cancer. Non-melanoma skin cancer, including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), is the most common form of skin cancer and accounts for 2-3 million worldwide cases of cancer each year. Smad4 loss occurs frequently in human skin squamous cell carcinoma (SCC), and we have shown that keratinocyte specific Smad4 deletion in K14.Smad4-/- mice leads to reduced expression of DNA repair genes, increased DNA damage and increased susceptibility to UV-induced SCC. Since UV-irradiation leads to oxidative damage to DNA, and unrepaired DNA damage may lead to cancer, so we tested if administration of an antioxidant, 4-hydroxy-tempo (tempol) in the diet of WT and K14.Smad4-/- mice reduces UV-induced skin carcinogenesis. In the present study, we divided WT and K14.Smad4-/- mice into two groups each, one group was fed tempol chow while the other group was fed control chow. All mice were exposed to chronic UV irradiation for 38 weeks from 3 months of age. Indeed, the tempol diet led to delayed onset and reduced number of skin tumors in K14.Smad4-/- mice. Tempol diet led to reduced 8-hydroxyguanosine staining, indicative of reduced oxidative DNA damage, as well as reduced cox-2 expression in the skin of K14.Smad4-/- mice compared to K14.Smad4-/- mice on control diet. It is plausible that reduced inflammation in these mice led to reduced carcinogenesis, these and other mechanisms are being investigated. Citation Format: Doyel Mitra, Bian Li, Qinghong Zhang, James B. Mitchell, Xiao-Jing Wang. Tempol diet provides chemoprotection against UV-induced skin cancer in mice with epidermal Smad4 deletion. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2258. doi:10.1158/1538-7445.AM2014-2258