Unrepaired Cyclobutane Pyrimidine Dimers Do Not Prevent Proliferation of UV-B–irradiated Cultured Human Fibroblasts¶
- 1 January 2004
- journal article
- research article
- Published by Wiley in Photochemistry and Photobiology
- Vol. 79 (2) , 145-51
- https://doi.org/10.1562/0031-8655(2004)079<0145:ucpddn>2.0.co;2
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 tandem 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 pyrimidines. 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 (−2) were chosen 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.Keywords
This publication has 49 references indexed in Scilit:
- Photoimmunology and nucleotide excision repair: impact of transcription coupled and global genome excision repairJournal of Photochemistry and Photobiology B: Biology, 2001
- The effects of the melatonin on ultraviolet-B irradiated cultured dermal fibroblastsJournal of Dermatological Science, 2001
- UV-induced DNA damage, repair, mutations and oncogenic pathways in skin cancerJournal of Photochemistry and Photobiology B: Biology, 2001
- Nucleotide excision repair and human syndromesCarcinogenesis: Integrative Cancer Research, 2000
- Transcription coupled repair and its impact on mutagenesisMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, 1998
- UV-induced mutagenesis in the endogenous hprt gene and in hprt cDNA genes integrated at different positions of the human genomeMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, 1995
- Specific UV-induced mutation spectrum in the p53 gene of skin tumors from DNA-repair-deficient xeroderma pigmentosum patients.Proceedings of the National Academy of Sciences, 1993
- Mutation hotspots due to sunlight in the p53 gene of nonmelanoma skin cancers.Proceedings of the National Academy of Sciences, 1993
- The distribution of UV damage in the lacI gene of Escherichia coli: Correlation with mutation spectrumMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, 1992
- The specificity of UV-induced mutations at an endogenous locus in mammalian cells.Proceedings of the National Academy of Sciences, 1987