Multiple forms of DNA Damage Caused by UVA Photoactivation of DNA 6-Thioguanine

被引：61

作者：

Brem, Reto ^{[1
]}

Karran, Peter ^{[1
]}

机构：

[1] Canc Res UK London Res Inst, Clare Hall Labs, S Mimms, Herts, England

来源：

PHOTOCHEMISTRY AND PHOTOBIOLOGY | 2012年 / 88卷 / 01期

关键词：

OXYGEN-MEDIATED DAMAGE; MISMATCH REPAIR; CROSS-LINKING; STRAND BREAKS; THIOPURINE; RADIATION; REPLICATION; OXIDATION; MERCAPTOPURINE; CELLS;

D O I：

10.1111/j.1751-1097.2011.01043.x

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Thiopurines are prescribed frequently as medication for cancer and for inflammatory disorders. One of them, azathioprine, has been the immunosuppressant of choice for organ transplant recipients for many years. Thiopurine use is associated with elevated sun sensitivity and skin cancer risk. Skin sensitization is selective for UVA. 6-TG integrates into DNA and unlike the canonical DNA bases, it is a strong UVA chromophore with an absorbance maximum at 342 nm. DNA 6-TG is a photosensitizer and a source of reactive oxygen species. Reactive oxygen that is generated from the photochemical activation of DNA 6-TG causes extensive damage to DNA and proteins. This damage is mutagenic and extremely toxic to cultured human cells. Here we describe some of the lesions that are known to be generated from UVA irradiation of DNA 6-TG. We discuss how this photochemical damage might contribute to the toxic effect of thiopurine/UVA treatment on cultured cells and to the high risk of skin cancer in thiopurine-treated patients.

引用

页码：5 / 13

页数：9

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