Guanine sulphinate is a major stable product of photochemical oxidation of DNA 6-thioguanine by UVA irradiation
Open accessAbstract
The DNA of patients taking the immunosuppressant and anticancer drugs azathioprine or 6-mercaptopurine contains 6-thioguanine (6-TG). The skin of these patients is selectively sensitive to ultraviolet A radiation (UVA) and they suffer an extremely high incidence of sunlight-induced skin cancer with long-term treatment. DNA 6-TG interacts with UVA to generate reactive oxygen species, which oxidize 6-TG to guanine sulphonate (G(SO3)). We suggested that G(SO3) is formed via the reactive electrophilic intermediates, guanine sulphenate (G(SO)) and guanine sulphinate (G(SO2)). Here, G(SO2) is identified as a significant and stable UVA photoproduct of free 6-TG, its 2'-deoxyribonucleoside, and DNA 6-TG. Mild chemical oxidation converts 6-TG into G(SO2), which can be further oxidized to G(SO3)-a stable product that resists further reaction. In contrast, G(SO2) is converted back to 6-TG under mild conditions. This suggests that cellular antioxidant defences might counteract the UVA-mediated photooxidation of DNA 6-TG at this intermediate step and ameliorate its biological effects. In agreement with this possibility, the antioxidant ascorbate protected DNA 6-TG against UVA oxidation and prevented the formation of G(SO3).
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Main DNA oxidation products from singlet oxygen oxidation of the thiol function of 6-TG are stable guanine 6-sulphinate and guanine 6-sulfonate via transient guanine 6-sulphenate.
“The main DNA oxidation products arise from 1 O 2 oxidation of the thiol function of 6-TG; they were characterized as stable guanine 6-sulphinate (G S02 ) and guanine 6-sulfonate (G S03 ) through initial transient guanine 6-sulphenate (G SO ) (212,213).”
From Photoinduced Damage to Cellular DNA: Direct and Photosensitized Reactions<sup>†</sup> (2012) · cites this paper as [213]
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Self-citation
- Authors
- Ren, X., Li, F., Jeffs, G., Zhang, X., Xu, Y.-Z., & Karran, P.
- Affiliations
- Cancer Research UK (GB)
- The Open University (GB)
- Corresponding author
- Karran, Peter
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-12-21
- Volume
- 38
- Issue
- 6
- Pages
- 1832-1840
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- PMC
- PMC2847230
- OpenAlex
- W2116165311
- Cited by
- 55
- References
- 17
- Citations by year
- 2025: 1 · 2022: 2 · 2021: 2 · 2020: 2 · 2019: 5 · 2018: 5 · 2017: 6 · 2016: 5 · 2015: 2 · 2014: 5 · 2013: 1 · 2012: 8
- FWCI
- 2.12
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Nucleic Acids Research (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Open Research Online (The Open University) (acceptedVersion)
- Funders
- Cancer Research UK (11584)
- Engineering and Physical Sciences Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Health Sciences › Medicine › Dermatology › Skin Protection and Aging
- Keywords
- 6-thioguanine, reactive oxygen species, azathioprine, 6-mercaptopurine, vitamin C, antioxidant defense, electrophilic intermediates
- MeSH terms
- Arylsulfonates, Ascorbic Acid, DNA, Guanine, Oxidation-Reduction, Sulfides, Thioguanine, Ultraviolet Rays, Photochemical Processes
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