17β‐Oestradiol attenuates nucleotide excision repair

FEBS Letters

Nicoll, Karen¹  Butler, John M¹  Evans, Mark D¹  Lunec, Joseph¹  Cooke, Marcus S¹ 

[1] Oxidative Stress Group, Department of Clinical Biochemistry, P.O. Box 65, Robert Kilpatrick Clinical Sciences Building, University of Leicester, Leicester Royal Infirmary, University Hospitals of Leicester NHS Trust, Leicester LE2 7LX, UK

关键词: Estradiol;    DNA repair;    Nucleotide excision repair;    Breast cancer;    Thymine dimer;    E2;    17β-oestradiol;    ER;    oestrogen receptor;    NER;    nucleotide excision repair;    T〈〉T;    cyclobutane thymine dimers;   

DOI  :  10.1016/S0014-5793(02)03898-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Epidemiological studies strongly suggest associations between chronic exposure to endogenous oestrogens and the development of breast and gynaecological tumours. Two mechanisms by which 17β-oestradiol (E₂) may enhance tumorigenesis are: (i) enhancement of cell proliferation and (ii) the production of reactive, genotoxic metabolites. Here we suggest an additional mechanism, inhibition of DNA repair. The removal of UV-induced thymine dimers from human keratinocytes, reflective of nucleotide excision repair, was significantly attenuated by treatment of cells with E₂. In contrast, treatment with 17α-oestradiol had no effect. Mechanisms are proposed for this effect of E₂, which may contribute to its carcinogenic potential.

【 授权许可】

Unknown