An understanding of the role of immunomodulation in reducing UV induced immunosuppression and in preventing photocarcinogenesis would add to our knowledge of host resistance factors against carcinogenesis and could aid in terms of prevention of malignancy. UVB induced immunosuppression is critical for the development of UVB induced skin tumors, and it is important to know if prevention of this immunosuppression results in host resistance to photocarcinogenesis. The mouse skin model of UVB tumorigenesis will be used in these studies because the kinetics of UV dosage, immunosuppression, and tumor formation have been delineated in this system. C3H/HeN mice will be treated for three weeks with selected doses of the immunomodulators: vitamin E, selenium, diethyldithiocarbamate, or recombinant interleukin-2. Combinations of the most chemopreventive agents at nontoxic doses will be investigated later in the study. After three weeks of exposure to immunomodulators, the mice will be UVB radiated dorsally to induce immunosuppression. Resistance of the treated mice to UV induced tumors will be assessed by measuring primary tumor growth and by measuring outgrowth of implanted antigenic, syngeneic UV induced tumor cells (UV22). The modulation of in vivo rejection will be studied by quantification of leukocyte subpopulations infiltrating into the UV22 tumor challenges. Unirradiated mice reject these tumors, whereas irradiated mice do not. Comparisons of leukocyte phenotypes in challenges of the same tumor (UV22), undergoing rejection versus acceptance should reveal which immunological cells are important for rejection. Immunosuppression will be assessed by the capacity of splenocytes from treated or untreated, UV irradiated mice to transfer suppression to naive mice. The ability of UVB irradiation to systemically effect the tumoricidal capacity of peritoneal macrophages, and the influence of immunomodulators on this effect, will be measured. These experiments should clarify whether prevention of immunosuppression will effectively prevent photocarcinogenesis.
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