There is a high incidence of non-melanoma skin cancers in man and patients who have had one such malignancy tend to get additional skin cancers. Retinoids and carotenoids have a proven capacity to reduce the formation of chemically-induced mouse skin tumors. In addition, dietary carotenoids have been shown to inhibit UVB induced mouse skin tumors; however, the ability of retinoids to inhibit UVB induced mouse skin tumors remains to be defined. We shall test the tumor preventing capacity of these agents by their administration in the diet before and during UVB irradiation. The duration of retinoid and carotenoid-induced tumor prevention after cessation of all treatments will be measured. We shall use Kripke's standardized tumor induction protocol in which T cell immunosuppression plays a critical role in tumor growth. We shall test the hypothesis that retinoids and carotenoids inhibit UVB-induced tumorigenesis because these agents are able to prevent suppression of immune functions in UVB irradiated mice by: a) reducing T suppressor cells, b) stimulating T helper cells, c) stimulating tumoricidal T cells, and/or d) activating macrophages and macrophage like Langerhans cells. Retinoids have been shown to prevent the immunosuppression induced in humans by thermal injury and by surgical trauma. UVB irradiation induces specific T suppressor cells and can serve as a system in which to study control of immunosuppression. The specific immunological parameters related to our hypothesis that will be studied include measurements of a) T lymphocyte helper: suppressor ratio in histological sections of the skin of retinoid or carotenoid-treated mice after UVB irradiation, b) the number and morphology of ADPase positive dendritic cells (as a measure of Langerhans cells) in the skin of retinoid or carotenoid-treated mice after UVB irradiation, and c) in vivo abrogation by dietary retinyl palmitate and carotenoid of UVB-induced T suppressor cells in the spleen, as determined by passive transfer of spleen cells to immunized syngeneic recipients. We believe that this research will clarify the roles of dietary retinoids and carotenoids in a) the prevention of UVB induced cutaneous cancer and b) the prevention of UVB-induced immunosuppression.
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