Chen W, Barthelman M, Martinez J, Alberts D, Gensler H L
Department of Radiation Oncology, College of Medicine, University of Arizona, Tucson 85724, USA.
Nutr Cancer. 1997;29(3):205-11. doi: 10.1080/01635589709514625.
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 alpha-tocopherol prevents UV-induced skin carcinogenesis in the mouse. In the present study we asked whether topical alpha-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 alpha-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 alpha-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 alpha-tocopherol treatment. Therefore, the lower level of cyclobutane pyrimidine dimers in UV-irradiated mice treated with alpha-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 alpha-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.
在人和动物中，50%-100%的紫外线（UV）诱导的鳞状细胞癌中都观察到了p53基因的突变或改变。大多数突变发生在二嘧啶序列处，这表明p53基因中的嘧啶二聚体在皮肤鳞状细胞癌的发病机制中起作用。我们之前表明，局部应用α-生育酚可预防小鼠UV诱导的皮肤癌发生。在本研究中，我们探讨局部应用α-生育酚是否能降低小鼠表皮p53基因中UV诱导的环丁烷嘧啶二聚体水平。在暴露于500 J/m2的UV-B辐射之前，小鼠背部每隔一天接受六次每次25 mg的α-生育酚涂抹。在辐射后的选定时间处死小鼠。使用T4内切酶V测定法和定量Southern杂交来测量表皮p53基因中二聚体的水平。局部应用α-生育酚使表皮p53基因中环丁烷嘧啶二聚体的形成减少了55%。在UV辐射后的小鼠中，无论是否用α-生育酚处理，照射后1至10小时之间嘧啶二聚体的减少速率相似。因此，用α-生育酚处理的UV辐射小鼠中环丁烷嘧啶二聚体水平低于对照UV辐射小鼠，这是由于二聚体形成的预防，而不是这些损伤修复的增强。我们的结果表明，α-生育酚在体内起到有效的防晒作用，可防止在一个已知对皮肤癌发生很重要的基因中形成致突变前的DNA损伤。
