Topical vitamin E inhibition of immunosuppression and tumorigenesis induced by ultraviolet irradiation

Ultraviolet (UV) irradiation of C3H/HeN mice induces skin cancer and an immunosuppression that prevents the host from rejecting antigenic UV-induced tumors. The capacity of topical vitamin E (dl-alpha-tocopherol) to prevent photocarcinogenesis or the immunosuppression induced by UV irradiation were assessed. Skin cancer incidence in UV-irradiated mice was 81% at 33 weeks after the first UV exposure; application to mice of 25 mg vitamin E three times per week for three weeks before UV irradiation, and throughout the experiment, reduced this incidence to 42% (p = 0.0065, log rank test). Immunoenhancement by vitamin E was assessed by comparing levels of immunosuppression by splenocytes from normal or UV-irradiated mice, with and without topical vitamin E treatment. Transfer of splenocytes from UV-irradiated mice to naive mice prevented the recipients from rejecting a UV-induced tumor challenge, whereas splenocytes from UV-irradiated mice treated with vitamin E did not prevent recipients from rejecting a similar tumor challenge. Phenotypic analysis of splenocytes used in the passive transfer assay, conducted with a biotin-avidin-immunoperoxidase technique, revealed that vitamin E treatment of mice undergoing UV irradiation prevented the UV-induced down regulation of Ia expression in splenocytes and increased the proportion of Lyt-2+ and L3T4+ splenocytes. Therefore, chronically applied vitamin E can effectively reduce cancer formation and immunosuppression induced by UV irradiation. Prevention of UV-induced down regulation of Ia expression may have contributed to this immunomodulation.