Inhibition of cyclobutane pyrimidine dimer formation in epidermal p53 gene of UV-irradiated mice by α-tocopherol

Weixing Chen, Margaret Barthelman, Jessie Martinez, David Alberts, Helen L. Gensler

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

Mutations or alterations in the p53 gene have been observed in 50-100% of ultraviolet light (UV)-induced squamous cell carcinoma in humans and animals. Most of the mutations occurred at dipyrimidine sequences, suggesting that pyrimidine dimers in the p53 gene play a role in the pathogenesis of cutaneous squamous cell carcinoma. We previously showed that topical α- tocopherol prevents UV-induced skin carcinogenesis in the mouse. In the present study we asked whether topical α-tocopherol reduces the level of UV- induced cyclobutane pyrimidine dimers in the murine epidermal p53 gene. Mice received six dorsal applications of 25 mg each of α-tocopherol, on alternate days, before exposure to 500 J/m2 of UV-B irradiation. Mice were killed at selected times after irradiation. The level of dimers in the epidermal p53 gene was measured using the T4 endonuclease V assay with quantitative Southern hybridization. Topical α-tocopherol caused a 55% reduction in the formation of cyclobutane pyrimidine dimers in the epidermal p53 gene. The rate of reduction of pyrimidine dimers between 1 and 10 hours after irradiation was similar in UV-irradiated mice, regardless of α-tocopherol treatment. Therefore, the lower level of cyclobutane pyrimidine dimers in UV- irradiated mice treated with α-tocopherol than in control UV-irradiated mice resulted from the prevention of formation of the dimers, and not from enhanced repair of these lesions. Our results indicate that α-tocopherol acts as an effective sunscreen in vivo, preventing the formation of premutagenic DNA lesions in a gene known to be important in skin carcinogenesis.

Original languageEnglish (US)
Pages (from-to)205-211
Number of pages7
JournalNutrition and cancer
Volume29
Issue number3
DOIs
StatePublished - Jan 1 1997

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Oncology
  • Nutrition and Dietetics
  • Cancer Research

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