Cited by 684Skin Protection and AgingDNA Repair MechanismsCarcinogens and Genotoxicity Assessment

Cyclobutane pyrimidine dimers are predominant DNA lesions in whole human skin exposed to UVA radiation

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Mouret, Stéphane, Baudouin, Caroline, Charveron, Marie, Favier, Alain, Cadet, Jean, Douki, Thierry·2006·Proceedings of the National Academy of Sciences

Abstract

Solar UV radiation is the most important environmental factor involved in the pathogenesis of skin cancers. The well known genotoxic properties of UVB radiation (290–320 nm) mostly involve bipyrimidine DNA photoproducts. In contrast, the contribution of more-abundant UVA radiation (320–400 nm) that are not directly absorbed by DNA remains poorly understood in skin. Using a highly accurate and quantitative assay based on HPLC coupled with tandem mass spectrometry, we determined the type and the yield of formation of DNA damage in whole human skin exposed to UVB or UVA. Cyclobutane pyrimidine dimers, a typical UVB-induced DNA damage, were found to be produced in significant yield also in whole human skin exposed to UVA through a mechanism different from that triggered by UVB. Moreover, the latter class of photoproducts is produced in a larger amount than 8-oxo-7,8-dihydro-2′-deoxyguanosine, the most common oxidatively generated lesion, in human skin. Strikingly, the rate of removal of UVA-generated cyclobutane pyrimidine dimers was lower than those produced by UVB irradiation of skin. Finally, we compared the formation yields of DNA damage in whole skin with those determined in primary cultures of keratinocytes isolated from the same donors. We thus showed that human skin efficiently protects against UVB-induced DNA lesions, whereas very weak protection is afforded against UVA. These observations emphasize the likely role played by the UVA-induced DNA damage in skin carcinogenesis and should have consequences for photoprotection strategies.

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Crossref · 10.1073/pnas.0604213103

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  • UVB irradiation of mammalian cells and human skin induces T<>T as the most frequent photoproduct.

    “For example, HPLC-ESI-MS ⁄ MS analysis showed that UVB irradiation of mammalian cells (53,54,56,60) and human skin (61) induces T<>T as the most frequent photoproduct.”
  • Calibrated immunoassays, electrophoretic analysis and chromatographic measurements give absolute lesion yields of 0.2 to 0.5 per 10^6 bases per J m^-2 upon UVB exposure of cultured cells.

    “In terms of absolute yields of lesions, calibrated immunoassays, electrophoretic analysis and chromatographic measurements lead to values ranging between 0.2 and 0.5 per 10 6 bases per J m )2 upon exposure of cultured cells to UVB (55,61,62).”
  • The yield of bipyrimidine photoproducts is much lower in skin than in cells, although the distribution is similar.

    “The yield of bipyrimidine photoproducts is much lower in skin than in cells, although the distribution of photoproducts is similar (61).”
  • UVA radiation has been shown since the 1970s to induce CPDs in bacteria, mammalian cells and human skin.

    “In fact, UVA radiation has been shown since the 1970s, first in bacteria (29) and then in mammalian cells (32,55,(80)(81)(82)(83)(84) and human skin (61,65,(85)(86)(87), to be also able to induce CPDs.”
  • The yield of UVA-induced CPDs is larger than that of oxidatively generated lesions such as 8-oxoGua.

    “As a striking information, the yield of CPDs was found to be larger than that of oxidatively generated lesions such as 8-oxoGua (32,46,61,88) that were long thought to be the hallmark of UVA genotoxicity, as further discussed below.”

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Authors
Mouret, S., Baudouin, C., Charveron, M., Favier, A., Cadet, J., & Douki, T.
Affiliations
  • Université Joseph Fourier (FR)
  • Laboratoire de Biologie Cellulaire, Institut de Recherche Pierre Fabre, Hôtel Dieu Saint Jean, 2 rue Viguerie, 31025 Toulouse Cedex 3, France
Venue
Proceedings of the National Academy of Sciences
Published
2006-09-12
Volume
103
Issue
37
Pages
13765-13770
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2087406053
Cited by
684
References
62
Citations by year
2026: 20 · 2025: 28 · 2024: 24 · 2023: 23 · 2022: 32 · 2021: 38 · 2020: 35 · 2019: 33 · 2018: 35 · 2017: 30 · 2016: 39 · 2015: 36 · 2014: 45 · 2013: 43 · 2012: 42
FWCI
33.90
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, other-oa)
Topics
  • Health Sciences › Medicine › Dermatology › Skin Protection and Aging
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
Keywords
cyclobutane pyrimidine dimers, UVA, UV-B radiation, DNA photoproducts, skin carcinogenesis, 8-oxo-7,8-dihydro-2'-deoxyguanosine, keratinocytes, photoprotection, solar ultraviolet radiation
MeSH terms
8-Hydroxy-2'-Deoxyguanosine, Cells, Cultured, Deoxyguanosine, DNA, DNA Damage, Humans, Pyrimidine Dimers, Skin, Ultraviolet Rays

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