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

被引:32
作者
Chen, WX
Barthelman, M
Martinez, J
Alberts, D
Gensler, HL [1 ]
机构
[1] Univ Arizona, Coll Med, Dept Radiat Oncol, Tucson, AZ 85724 USA
[2] Univ Arizona, Coll Med, Arizona Canc Ctr, Canc Prevent & Control Program, Tucson, AZ 85724 USA
[3] Univ Arizona, Coll Med, Dept Med, Sect Hematol & Oncol, Tucson, AZ 85724 USA
来源
NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL | 1997年 / 29卷 / 03期
关键词
D O I
10.1080/01635589709514625
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 W-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/m(2) 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 I 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.
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页码:205 / 211
页数:7
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