Ultraviolet light B (UVB) is ubiquitous and a complete carcinogen for skin cancer. UVB-induced inflammation is a critical step in skin carcinogenesis. Preventive options include sun avoidance, sunblock use, and anti-inflammatory agents. The anti-inflammatory effects of dietary n-3 polyunsaturated fatty acids (PUFAs) have been observed in several inflammatory diseases, including UVB-induced skin damage. Peroxisome proliferator activated receptor gamma (PPARγ) is a steroid nuclear receptor activated by specific fatty acids and synthetic ligands that is also associated with anti-inflammatory responses. To test the hypothesis that the preventive properties of n-3 PUFAs may in part act through the PPARγ signaling pathway, we conducted a study of dietary fish oil vs. corn oil (25% of energy) with or without rosiglitazone in the hairless SKH-1 mouse model of skin carcinogenesis. A control group fed standard lab chow was included. After 6 weeks of diet, the mice were exposed to one dose of UVB (2240 J/m2) to induce an inflammatory response (sunburn) and sacrificed 48hrs later. In response to UVB, all mice showed increased skin thickness as a measure of edema and clinical marker of inflammation. Fish oil (FO) mice had the thinnest skin of all UVB-exposed mice. Fish oil+rosiglitazone (FOR) mice had significantly thicker skin than FO mice (p<0.04). Using Ly6G+ cells in the dermis as an immunohistochemical measurement for neutrophil infiltration and the myeloperoxidase (MPO) assay as a biochemical measurement of neutrophil activity, we determined that UVB increased both neutrophil infiltration and activity in the skin of mice in all diet groups. Although FO and FOR mice had the lowest number of neutrophils in the dermis with no UVB exposure, FO mice had the highest number of neutrophils in the dermis with UVB exposure. Corn oil (CO) mice had the lowest dermal neutrophil count. Skin samples from UVB-treated FO mice had significantly increased levels of myeloperoxidase activity relative to UVB-exposed CO mice (p<0.03). Our data demonstrate differential effects of dietary fish oil and corn oil on clinical and biochemical indices of skin inflammation in SKH-1 mice following UVB exposure, with possible attenuation of n-3 PUFA-mediated effects by rosiglitazone. Further studies are needed to determine the mechanism by which fish oil can reduce UVB-induced edema but cause increased neutrophil invasion and activation in the skin. Given the prevalence of sun (UVB) exposure and skin cancer, the role of n-3 PUFAs and PPARγ activation in modulating UVB-exposed skin inflammation and potentially skin carcinogenesis requires further investigation.

[Proc Amer Assoc Cancer Res, Volume 47, 2006]