Unrepaired Cyclobutane Pyrimidine Dimers Do Not Prevent Proliferation of UV‐B‐irradiated Cultured Human Fibroblasts¶
Abstract
Mutagenic and carcinogenic UV‐B radiation is known to damage DNA mostly through the formation of bipyrimidine photoproducts, including cyclobutane dimers (CPD) and (6‐4) photoproducts ((6‐4) PP). Using high‐performance liquid chromatography coupled to tendem mass spectrometry, we investigated the formation and repair of thymine‐thymine (TT) and thymine‐cytosine (TC) CPD and (6‐4) PP in the DNA of cultured human dermal fibroblasts. A major observation was that the rate of repair of the photoproducts did not depend on the identity of the modified phyrimidines. In addition, removal of CPD was found to significantly decrease with increasing applied UV‐B dose, whereas (6‐4) PP were efficiently repaired within less than 24 h, irrespective of the dose. As a result, a relatively large amount of CPD remained in the genome 48 h after the irradiation. Because the overall applied doses (<500 J m−2) were chose to induce moderate cytotoxicity, fibroblasts could recover their proliferation capacities after transitory cell cycle arrest, as shown by 5‐bromo‐2′‐deoxyuridine (BrdUrd) incorporation and flow cytometry analysis. It could thus be concluded that UV‐B‐irradiated cultured primary human fibroblasts normally proliferate 48 h after irradiation despite the presence of high levels of CPD in their genome. These observations emphasize the role of CPD in the mutagenic effects of UV‐B.
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From Photoinduced Damage to Cellular DNA: Direct and Photosensitized Reactions<sup>†</sup> (2012) · cites this paper as [60]
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- Authors
- Courdavault, S., Baudouin, C., Sauvaigo, S., Mouret, S., Candéias, S., Charveron, M., Favier, A., Cadet, J., & Douki, T.
- Affiliations
- Commissariat à l'Énergie Atomique et aux Énergies Alternatives (FR)
- Université Joseph Fourier (FR)
- Inserm (FR)
- Corresponding author
- Douki, Thierry
- ORCID
- Venue
- Photochemistry and Photobiology
- Publisher
- Wiley
- Published
- 2004-02
- Volume
- 79
- Issue
- 2
- Pages
- 145-151
- ISSN
- 0031-8655 (ISSN-L)
- 1751-1097
- OpenAlex
- W4206888154
- Cited by
- 12
- References
- 53
- Citations by year
- 2022: 1 · 2021: 2 · 2020: 1 · 2017: 1 · 2016: 2 · 2012: 1
- FWCI
- 0.24
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Photochemistry and Photobiology (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Health Sciences › Medicine › Dermatology › Skin Protection and Aging
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
- Keywords
- cyclobutane pyrimidine dimers, 6-4 photoproducts, UV-B radiation, DNA repair, human dermal fibroblasts, cell proliferation, thymine-thymine dimers, mutagenicity, cell cycle arrest, DNA damage
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Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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