PREVENTION OF PHOTOIMMUNOSUPPRESSION AND PHOTOCARCINOGENESIS BY TOPICAL NICOTINAMIDE

Ultraviolet (UV) B irradiation leads to a potent immunosuppression of the capacity to reject syngeneic, antigenic tumors. If this immunosupp ression is critical for the development of most skin tumors, then its prevention should result in prevention of photocarcinogenesis. We prev iously showed a correlation between the inhibition of photoimmunosuppr ession and prevention of photocarcinogenesis by dl-alpha-tocopherol, t annic acid, or alpha-difluoromethylornithine. The current study was de signed to determine whether topical nicotinamide, the active form of v itamin B-3, or niacin, prevents immunosuppression and skin cancer in U V-irradiated mice. In a passive transfer assay for immunosuppression, splenocytes from UV-irradiated mice enhanced the growth of antigenic t urner challenges in recipient mice. Treatment of the UV-irradiated mic e with 40 mu mol of nicotinamide twice weekly starting two weeks befor e UV irradiation and throughout the experiment prevented this immunosu ppression. UVB irradiation consisted of five weekly 30-minute exposure s to banks of six FS40 Westinghouse fluorescent sunlamps. Mice receive d approximately 6.2 x 10(5) J/m(2) in the passive transfer assays and 1.09 x 10(6) J/m(2) in the photocarcinogenesis studies. Application of nicotinamide to UV-irradiated mice reduced skin tumor incidence from 75% to 42.5% (p = 0.016, Cox proportional hazards analysis). Thus topi cal nicotinamide prevented the immunosuppression and skin tumor-induct ion by UVB irradiation.