Demonstration of UV-dimers in human skin DNA in situ 3 weeks after exposure

被引:21
作者
Hemminki, K [1 ]
Xu, GG
Kause, L
Koulu, LM
Zhao, CY
Jansen, CT
机构
[1] Karolinska Inst, Novum, Dept Biosci, S-14157 Huddinge, Sweden
[2] Univ Turku, Dept Dermatol, Turku 20520, Finland
关键词
D O I
10.1093/carcin/23.4.605
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Data on DNA repair rates of specific types of DNA lesions are very limited in humans in situ. Rate of repair of UV-induced DNA damage was followed in the skin of 17 volunteers up to 3 weeks of UV exposure, using a P-32-postlabelling technique for the determination of specific photoproducts. The subjects of skin phototypes I and IV were exposed to 40 mJ/cm(2) of solar simulating radiation on buttock skin, and biopsies were taken at 0 h, 48 h and 3 weeks of exposure for the analysis of two cyclobutane pyrimidine dimers, TT=C and TT=T, and two 6-4 photoproducts, TT-C and TT-T, as trinucleotides. Repair rates were heterogeneous for different photoproducts. T=T dimers were repaired slower than C=T dimers, and 2.3-9.0% of the initial T=T damage remained unrepaired after 3 weeks, and was detectable in 16/17 subjects. The identity of the identified photoproducts was confirmed by a photochemical reversion assay. Damage level correlated with skin types, type I being more sensitive than type IV in an age-matched comparison. This is the first time the persistence of defined human DNA damage is demonstrated up to 3 weeks. Long-lasting DNA damage increases the likelihood of mutations.
引用
收藏
页码:605 / 609
页数:5
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