Importance of the form of topical vitamin E for prevention of photocarcinogenesis

Abstract

With increasing solar ultraviolet (UV)‐B radiation reaching the Earth's surface and the incidence of skin cancer rising steadily, there is an ever‐increasing need to determine agents that modulate photocarcinogenesis and to understand the mechanisms underlying this modulation. Our laboratory has demonstrated that topical application of the dl‐α‐tocopherolform of vitamin E to mice prevents skin cancer and the immunosuppression induced by UVB irradiation. However, dl‐α‐tocopherol has limited stability at room temperature. The current study was designed to ask whether the thermostable esters of vitamin E, α‐tocopheryl acetate, or α‐tocopheryl succinate prevent skin cancer and immunosuppression induced in mice by UV radiation. In the α‐tocopheryl acetate study, skin cancers developed in 70% of UVB‐irradiated control mice and in 90%, 73%, and 90% of mice receiving topical applications of 12.5, 25, and 50 mg of dl‐α‐tocopheryl acetate, respectively. In the α‐tocopheryl succinate study, skin cancer developed in 59.3% of control UVB‐irradiated mice and in 82%, 100%, and 81.5% of mice treated with 2.5, 12.5, and 25 mg d‐α‐tocopheryl succinate, respectively. Thus neither α‐tocopheryl acetate nor α‐tocopheryl succinate prevented photocarcinogenesis. At 12.5 and 25 mg/treatment, α‐tocopheryl acetate and α‐tocopheryl succinate, respectively, enhanced photocarcinogenesis (p = 0.0114 and 0.0262, respectively, log rank test). On the basis of high‐performance liquid chromatography analysis at 16–17 weeks after the first vitamin E treatment, the esterifled forms of vitamin E applied epicutaneously accumulated in the skin, but the levels of free α‐tocopherol remained low. Neither α‐tocopheryl acetate nor α‐tocopheryl succinate prevented the induction by UV radiation of immunosusceptibility to implantedsyngeneic antigenic UV‐induced tumor cells. Thus α‐tocopheryl acetate or α‐tocopheryl succinate not only failed to prevent photocarcinogenesis, but may have enhanced the process. Considering that α‐tocopherol esters are included in many skin lotions, cosmetics, and sunscreens, further studies are needed to determine the conditions under which topical α‐tocopheryl acetate and α‐tocopheryl succinate enhance photocarcinogenesis.