Cyclobutane pyrimidine dimers are predominant DNA lesions in whole human skin exposed to UVA radiation
Open accessAbstract
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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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.”
From Photoinduced Damage to Cellular DNA: Direct and Photosensitized Reactions<sup>†</sup> (2012) · cites this paper as [61]
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).”
From Photoinduced Damage to Cellular DNA: Direct and Photosensitized Reactions<sup>†</sup> (2012) · cites this paper as [61]
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).”
From Photoinduced Damage to Cellular DNA: Direct and Photosensitized Reactions<sup>†</sup> (2012) · cites this paper as [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.”
From Photoinduced Damage to Cellular DNA: Direct and Photosensitized Reactions<sup>†</sup> (2012) · cites this paper as [61]
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.”
From Photoinduced Damage to Cellular DNA: Direct and Photosensitized Reactions<sup>†</sup> (2012) · cites this paper as [61]
Neither 6-4PPs nor Dewar valence isomers have been observed by specific chromatographic techniques after UVA exposure, even at high doses.
“Although tiny amounts of 6-4PPs have been detected by immunological assays (55), neither the formation of this class of damage nor of DEWs has been observed using more specific chromatographic techniques, even at high doses of UVA (46,61,88).”
From Photoinduced Damage to Cellular DNA: Direct and Photosensitized Reactions<sup>†</sup> (2012) · cites this paper as [61]
8-oxoGua is generated in significant yields upon UVA exposure of cultured cells and skin.
“A much more common biomarker of oxidatively generated damage to DNA is 8-oxoGua that has been found to be generated in significant yields upon exposure of cultured cells (85,112,113) and skin (61) to UVA radiation.”
From Photoinduced Damage to Cellular DNA: Direct and Photosensitized Reactions<sup>†</sup> (2012) · cites this paper as [61]
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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
- Publisher
- National Academy of Sciences
- Published
- 2006-09-12
- Volume
- 103
- Issue
- 37
- Pages
- 13765-13770
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC1564232
- 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
- green
- europepmc.org
- 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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