The Open UniversitySkip to content

Novel DNA lesions generated by the interaction between therapeutic thiopurines and UVA light

Zhang, Xiaohong; Jeffs, Graham; Ren, Xiaolin; O'Donovan, Peter; Montaner, Beatriz; Perrett, Conal M.; Karran, Peter and Xu, Yao-Zhong (2007). Novel DNA lesions generated by the interaction between therapeutic thiopurines and UVA light. DNA Repair, 6(3) pp. 344–354.

DOI (Digital Object Identifier) Link:
Google Scholar: Look up in Google Scholar


The therapeutic effect of the thiopurines, 6-thioguanine (6-TG), 6-mercaptopurine, and its prodrug azathioprine, depends on the incorporation of 6-TG into cellular DNA. Unlike normal DNA bases, 6-TG absorbs UVA radiation, and UVA-mediated photochemical damage of DNA 6-TG has potentially harmful side effects. When free 6-TG is UVA irradiated in solution in the presence of molecular oxygen, reactive oxygen species are generated and 6-TG is oxidized to guanine-6-sulfonate (GSO3) and guanine-6 thioguanine in reactions involving singlet oxygen. This conversion is prevented by antioxidants, including the dietary vitamin ascorbate. DNA GSO3 is also the major photoproduct of 6-TG in DNA and it can be selectively introduced into DNA or oligonucleotides in vitro by mild chemical oxidation. Thermal stability measurements indicate that GSO3 does not form stable base pairs with any of the normal DNA bases in duplex oligonucleotides and is a powerful block for elongation by Klenow DNA polymerase in primer extension experiments. In cultured human cells, DNA damage produced by 6-TG and UVA treatment is associated with replication inhibition and provokes a p53-dependent DNA damage response.

Item Type: Journal Item
ISSN: 1568-7864
Keywords: 6-Thioguanine; Ultraviolet light; Photochemistry; Oxidative DNA damage; Antioxidants; Guanine-6-sulfonate; Reactive oxygen species; Rose Bengal; UVA; DNA photoproducts;
Academic Unit/School: Faculty of Science, Technology, Engineering and Mathematics (STEM) > Life, Health and Chemical Sciences
Faculty of Science, Technology, Engineering and Mathematics (STEM)
Item ID: 7116
Depositing User: Yao Xu
Date Deposited: 12 Mar 2007
Last Modified: 07 Dec 2018 09:02
Share this page:


Altmetrics from Altmetric

Citations from Dimensions

Actions (login may be required)

Policies | Disclaimer

© The Open University   contact the OU