Cited by 95Skin Protection and AgingNonmelanoma Skin Cancer StudiesCarcinogens and Genotoxicity Assessment

UVA photosensitization of thiopurines and skin cancer in organ transplant recipients

Attard, Natalie R., Karran, Peter·2012·Photochemical & Photobiological Sciences

Abstract

The thiopurines azathioprine, 6-mercaptopurine and 6-thioguanine (6-TG) are important medications for cancer and inflammatory disorders. They are also widely prescribed as immunosuppressants in organ transplant patients. Their metabolism results in the incorporation of 6-TG into patients' DNA, and this increases skin sensitivity to incident UVA. Unlike the canonical DNA bases, which do not absorb UVA to a significant degree, DNA 6-TG is a strong UVA chromophore. It acts as a Type II UVA photosensitizer, and the combination of 6-TG and UVA treatment induces a synergistic toxicity in cultured human cells. Here, we review some of the damage that this interaction causes. Photochemical activation of DNA 6-TG triggers DNA and protein oxidation; it induces DNA breakage, DNA crosslinking, oxidation of DNA bases and the covalent attachment of proteins to DNA. Many of these photochemical DNA lesions are difficult for cells to deal with, and we review the evidence linking thiopurine immunosuppression with genome instability and the high incidence of skin cancer in organ transplant recipients.

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Registry

Crossref · 10.1039/c1pp05194f

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41 of 41 references verified0 citation errors · 0 not checkable

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  • Formation yields of stable single oxidation products including GSO2, GSO3, and 8-oxoGua in 6-TG containing isolated and cellular DNA are not available so far.

    “However, the formation yields of stable single oxidation products, including G S02 , G S03 and 8-oxoGua (206) in 6-TG containing isolated and cellular DNA are not available so far.”
  • Long-term use of thiopurines is associated with a significant increase in incidence of skin squamous carcinoma in relation to solar radiation exposure, particularly in transplant recipients.

    “However, a significant increase in the incidence of skin squamous carcinoma has been shown to be associated with long-term use of thiopurines in relation to solar radiation exposure, particularly in transplant patient recipients (204,206).”

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Authors
Attard, N. R., & Karran, P.
Affiliations
Cancer Research UK (GB)
Venue
Photochemical & Photobiological Sciences
Published
2012-11
Volume
11
Issue
1
Pages
62-68
ISSN
  • 1474-905X (ISSN-L)
  • 1474-9092
OpenAlex
W2163768346
Cited by
94
References
41
Citations by year
2026: 4 · 2025: 7 · 2024: 1 · 2023: 4 · 2022: 7 · 2021: 9 · 2020: 3 · 2019: 6 · 2018: 5 · 2017: 12 · 2016: 5 · 2015: 4 · 2014: 8 · 2013: 6 · 2012: 11
FWCI
10.98
Type
journal article
Language
en
Open access
closed
Locations
  • Photochemical & Photobiological Sciences (publishedVersion)
  • PubMed (publishedVersion)
Funders
Cancer Research UK (11584)
Topics
  • Health Sciences › Medicine › Dermatology › Skin Protection and Aging
  • Health Sciences › Medicine › Epidemiology › Nonmelanoma Skin Cancer Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
Keywords
thiopurines, 6-thioguanine, azathioprine, 6-mercaptopurine, skin cancer, organ transplant recipients, immunosuppression, DNA oxidation, DNA cross-linking, genomic instability, DNA photodamage
MeSH terms
Azathioprine, Humans, Immunosuppressive Agents, Skin Neoplasms, Thioguanine, Ultraviolet Rays, Mercaptopurine, Photosensitizing Agents

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