DNA damage and immunosuppressive cytokines induced by ultraviolet radiation and chemical carcinogen

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Ultraviolet radiation(UVR) plays a major role in the development of skin cancers. We have previously reported that a model mice(XPA -/-) of xeroderma pigmentosum group A easily developed skin cancers by exposure to a small amount of UVB or chemical carcinogen(DMBA). DNA damages can cause mutations of tumor suppressor genes or oncogenes. Tumor immunity is important for cancer development and growth. We have demonstrated that contact hypersensitivity and tumor immunity were greatly suppressed by UVR and DMBA in XPA(-/-) mice. Transplanted tumor cells were rejected immunologically from wild type mice as well as XPA(-/-) mice unless exposed to UVB. On the other hand, tumor cells, which were injected into the UVB-irradiated skin of XPA mice, were not rejected and grew to a large tumor. In the present study, we investigated the soluble factors or cytokines which are involved in the UVR-induced immunosuppression. UVB-or DMBA-induced inflammation and immunosuppression were ablogated by pre-treatment of indomethacin which is an inhibitor of prostaglandin synthesis. We further demonstrated that in XPA(-/-)/mice, UVR and DMBA greatly stimulated the expression of mRNA of cyclooxygenase 2,IL-10 and TNFα which have immunosuppressive abilities. These results indicate that DNA damage stimulate the production of immunosuppressive factors and impairs tumor immunity.