Multiple forms of DNA Damage Caused by UVA Photoactivation of DNA 6‐Thioguanine
Open accessAbstract
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.
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Thiopurines are metabolized and incorporated into DNA as 6-thio-2'-deoxyguanosine, an efficient endogenous Type I and Type II photosensitizer absorbing UVA with maximum at 342 nm.
“This is explained by the metabolization and incorporation of thiopurines into DNA as 6-thio-2¢-deoxyguanosine, an efficient endogenous Type I and Type II photosensitizer absorbing in the UVA range with a maximum at 342 nm (209).”
From Photoinduced Damage to Cellular DNA: Direct and Photosensitized Reactions<sup>†</sup> (2012) · cites this paper as [209]
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- Authors
- Brem, R., & Karran, P.
- Affiliations
- Cancer Research UK (GB)
- Corresponding author
- Brem, Reto
- ORCID
- Brem, Reto
- Venue
- Photochemistry and Photobiology
- Publisher
- Wiley
- Published
- 2011-12-16
- Volume
- 88
- Issue
- 1
- Pages
- 5-13
- ISSN
- 0031-8655 (ISSN-L)
- 1751-1097
- OpenAlex
- W1520599316
- Cited by
- 76
- References
- 55
- Citations by year
- 2026: 1 · 2025: 7 · 2024: 2 · 2023: 2 · 2022: 7 · 2021: 5 · 2020: 6 · 2019: 5 · 2018: 4 · 2017: 5 · 2016: 6 · 2015: 2 · 2014: 6 · 2013: 10 · 2012: 8
- FWCI
- 0.56
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Photochemistry and Photobiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Cancer Research UK (11584)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
- Health Sciences › Medicine › Dermatology › Skin Protection and Aging
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Keywords
- 6-thioguanine, thiopurines, azathioprine, DNA damage, photosensitizers, reactive oxygen species, skin cancer risk, sun sensitivity, skin sensitization, mutagenicity, cytotoxicity, chromophores
- MeSH terms
- DNA Damage, Photochemistry, Thioguanine, Ultraviolet Rays, Reactive Oxygen Species
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