Cited by 76Carcinogens and Genotoxicity AssessmentSkin Protection and AgingDNA Repair Mechanisms

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

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Brem, Reto, Karran, Peter·2012·Photochemistry and Photobiology

Abstract

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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Crossref · 10.1111/j.1751-1097.2011.01043.x

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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).”

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  1. [23]23. Hemmens, V. J. and D. E. Moore (1984) Photo-oxidation of 6mercaptopurine in aqueous solution. Chem. Soc. Perkin. Trans. II , 209-211.
  2. [49]49. Li, F. (2010) DNA damage and UVA-induced oxidation of DNA 6-thioguanine. Ph.D. thesis, University College London.
  3. [57]57. Hofbauer, G. F. L., G. Straub, P. Dziunycz, R. Meyer, P. Karran, N. Attard, Y. Kamenisch, M. Berneburg, L. E. French, R. P. Wuthrich and A. L. Serra (2011) Switching from azathioprine to mycophenolate mofetil improves skin photosensitivity in kidney transplant recipients. Am. J. Transplant. , doi: 10.1111/j.1600-6143. 2011.03751.x. · DOI

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Authors
Brem, R., & Karran, P.
Affiliations
Cancer Research UK (GB)
Corresponding author
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
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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