UVA photosensitization of thiopurines and skin cancer in organ transplant recipients
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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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.”
From Photoinduced Damage to Cellular DNA: Direct and Photosensitized Reactions<sup>†</sup> (2012) · cites this paper as [206]
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).”
From Photoinduced Damage to Cellular DNA: Direct and Photosensitized Reactions<sup>†</sup> (2012) · cites this paper as [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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