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Carcinogenesis, Vol. 21, No. 10, 1801-1807, October 2000
© 2000 Oxford University Press

Cancer Biology

Enhanced tumor growth in UV-irradiated skin is associated with an influx of inflammatory cells into the epidermis

Ronald Sluyter and Gary M. Halliday1

Department of Medicine (Dermatology), Melanoma and Skin Cancer Research Institute, University of Sydney at Royal Prince Alfred Hospital, NSW 2006, Sydney, Australia

UV radiation causes a number of cellular changes within the skin which play a role in tumor outgrowth, including immunosuppression and production of growth-enhancing cytokines. Both of these enable tumors to grow but their relative importance in carcinogenesis is poorly defined. In this study, C3H/HeN mice were exposed to a single inflammatory dose of 410 mJ/cm2 UVB radiation (plus 100 mJ/cm2 UVA radiation) followed by the inoculation of a regressor squamous cell carcinoma into or the painting of oxazolone onto the treated skin. Tumors transplanted 2 or 3 but not 4 days after irradiation had a significantly higher growth rate than tumors inoculated into unirradiated control mice. In contrast, mice failed to respond to hapten when it was applied 2, 3 or 4 days after irradiation. Cytofluorimetric analysis demonstrated that the number of F4/80+ Langerhans cells was not significantly reduced until 4 days after irradiation, while the number of dendritic epidermal T cells was significantly lower at all time points observed after UV-irradiation. Furthermore, a large cellular infiltration of CD11b+, Gr-1+, CD45+ MHC class II+ and CD45+ MHC class II– cells into the epidermis was observed 2 and 3 days after irradiation, which corresponded with the enhanced tumor growth. To a lesser extent tumor growth was also associated with CD45+ MHC class IIhi cells, possibly the previously described UV-induced macrophage. In contrast, suppression of contact hypersensitivity corresponded with the reduction in dendritic epidermal T cells but not with other cell changes. The results suggest that, in this model, where immunosuppression did not appear to be responsible for enhanced tumor growth, inflammatory infiltrates may contribute to the promotion of skin tumor growth within UV-irradiated skin.


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