Abstract 4202: Sex disparities in the cutaneous response to acute ultraviolet light exposure

Abstract

Abstract Epidemiological evidence has identified a 3-fold increase in squamous cell skin cancer incidence in men compared to women. The historical explanation for this sex-bias is increased occupational exposure to ultraviolet (UV) light. Our studies demonstrated, however, that when chronically exposed to equivalent doses of UV light, male mice developed more skin tumors that were larger and more aggressive than those arising in female mice. Additionally, the skin of male mice acutely exposed to UV light had higher levels of oxidative DNA damage and decreased total antioxidant capacity compared to females (Thomas-Ahner, JM Cancer Research 2007). The hypothesis for the current study is that the topical application of anti-inflammatory and/or antioxidant compounds may differentially affect the acute UVB induced inflammatory response in the sexes. To test this hypothesis, female and male Skh-1 mice were exposed to 2240J/m2 UVB light followed immediately by topical application of either an anti-inflammatory compound (Solaraze), an antioxidant (Vitamin E), or a combination of the 2 compounds. Animals were sacrificed at 24 and 48 hrs following a single exposure and topical treatment. Skin was analyzed for myeloperoxidase (MPO) activity as a measure of neutrophil infiltration, catalase activity, and immunohistochemically for the presence of p53 protein in the epidermis. In response to UVB exposure, vehicle treated female mice had significantly increased MPO activity compared to male mice. Topical treatments with Solaraze, Vitamin E or the combination significantly reduced MPO levels in female mice but had no effects on the already low levels of UV-induced MPO in male skin. Catalase is a key enzyme used for detoxifying hydrogen peroxide in the skin. Baseline levels of catalase were lower in male skin compared to female skin and UVB exposure significantly reduced catalase in both sexes. Topical treatment with Solaraze significantly increased male catalase activity to levels similar to female unirradiated skin while vitamin E partially restored catalase activity in female mice but had no effect in male skin. The single exposure to UVB induced higher numbers of p53 positive epidermal cells in male skin, however at this time point topical treatment had no effect on UVB-induced p53 levels in either sex. Our data suggests that UVB differentially effects inflammation in the sexes and that topical application of anti-inflammatory or anti-oxidant compounds have differential effects on markers of an acute inflammatory response in the skin. Future studies will evaluate the effects of additional compounds and delivery vehicles following both acute and chronic UVB exposure. This work was supported by NIH NCI CA133629. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4202.