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

Nutr Cancer. 1996;26(2):183-91. doi: 10.1080/01635589609514474.


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-alpha-tocopherol form of vitamin E to mice prevents skin cancer and the immunosuppression induced by UVB irradiation. However, dl-alpha-tocopherol has limited stability at room temperature. The current study was designed to ask whether the thermostable esters of vitamin E, alpha-tocopheryl acetate, or alpha-tocopheryl succinate prevent skin cancer and immunosuppression induced in mice by UV radiation. In the alpha-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-alpha-tocopheryl acetate, respectively. In the alpha-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-alpha-tocopheryl succinate, respectively. Thus neither alpha-tocopheryl acetate nor alpha-tocopheryl succinate prevented photocarcinogenesis. At 12.5 and 25 mg/treatment, alpha-tocopheryl acetate and alpha-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 esterified forms of vitamin E applied epicutaneously accumulated in the skin, but the levels of free alpha-tocopherol remained low. Neither alpha-tocopheryl acetate nor alpha-tocopheryl succinate prevented the induction by UV radiation of immunosusceptibility to implanted syngeneic antigenic UV-induced tumor cells. Thus alpha-tocopheryl acetate or alpha-tocopheryl succinate not only failed to prevent photocarcinogenesis, but may have enhanced to process. Considering that alpha-tocopherol esters are included in many skin lotions, cosmetics, and sunscreens, further studies are needed to determine the conditions under which topical alpha-tocopheryl acetate and alpha-tocopheryl succinate enhance photocarcinogenesis.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Topical
  • Animals
  • Esterification
  • Female
  • Immunity / drug effects
  • Immunity / radiation effects
  • Mice
  • Mice, Inbred BALB C
  • Radiation-Protective Agents*
  • Skin / immunology
  • Skin / metabolism
  • Skin Neoplasms / chemically induced
  • Skin Neoplasms / etiology
  • Skin Neoplasms / prevention & control*
  • Specific Pathogen-Free Organisms
  • Tocopherols
  • Ultraviolet Rays / adverse effects*
  • Vitamin E / adverse effects
  • Vitamin E / analogs & derivatives
  • Vitamin E / metabolism
  • Vitamin E / therapeutic use*
  • alpha-Tocopherol* / analogs & derivatives*


  • Radiation-Protective Agents
  • Vitamin E
  • alpha-Tocopherol
  • Tocopherols