The specificity of UVA-induced DNA damage in human melanocytes
Abstract
Exposure to solar UV radiation is the origin of most skin cancers, including deadly melanomas. Melanomas are quite different from keratinocyte-derived tumours and exhibit a different mutation spectrum in the activated oncogenes, possibly arising from a different class of DNA damage. In addition, some data suggest a role for UVA radiation in melanomagenesis. To get further insight into the molecular mechanisms underlying induction of melanoma, we quantified a series of UV-induced DNA damage in primary cultures of normal human melanocytes. The results were compared with those obtained in keratinocytes from the same donors. In the UVB range, the frequency and the distribution of pyrimidine dimers was the same in melanocytes and keratinocytes. UVA was also found to produce thymine cyclobutane dimer as the major DNA lesion with an equal efficiency in both cell types. In contrast, following UVA-irradiation a large difference was found for the yield of 8-oxo-7,8-dihydroguanine; the level of this product was 2.2-fold higher in melanocytes than in keratinocytes. The comet assay showed that the induction of strand breaks was equally efficient in both cell types but that the yield of Fpg-sensitive sites was larger in melanocytes. Our data show that, upon UVA irradiation, oxidative lesions contribute to a larger extent to DNA damage in melanocytes than in keratinocytes. We also observed that the basal level of oxidative lesions was higher in the melanocytes, in agreement with a higher oxidative stress that may be due to the production of melanin. The bulk of these results, combined with qPCR and cell survival data, may explain some of the differences in mutation spectrum and target genes between melanomas and carcinomas arising from keratinocytes.
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In melanocytes, a CPD/8-oxoGua ratio of 1.4 reflects a larger oxidative stress.
“There is however an exception for melanocytes where a CPD ⁄ 8-oxoGua ratio 1.4 reflects the occurrence of a larger oxidative stress (89).”
From Photoinduced Damage to Cellular DNA: Direct and Photosensitized Reactions<sup>†</sup> (2012) · cites this paper as [89]
Melanocytes are more susceptible than other cell types to UVA-induced oxidative DNA damage, both as isolated cells and in pigmented mice.
“This was recently illustrated for melanocytes that are more susceptible than other cell types to UVA-induced oxidatively generated damage to DNA both as isolated cells (89,116) and in pigmented mice (117).”
From Photoinduced Damage to Cellular DNA: Direct and Photosensitized Reactions<sup>†</sup> (2012) · cites this paper as [89]
Cites
Mutations of the BRAF gene in human cancer
Davies, H., Bignell, G. R., Cox, C., Stephens, P., Edkins, S., Clegg, S., Teague, J., Woffendin, H., Garnett, M. J., Bottomley, W., et al. (2002) · Nature · doi:10.1038/nature00766 · Cited by 10,674 · see citing works
Pfaffl, M. W. (2002) · Nucleic Acids Research · doi:10.1093/nar/30.9.e36 · Cited by 7,377 · see citing works
Distinct Sets of Genetic Alterations in Melanoma
Curtin, J. A., Fridlyand, J., Kageshita, T., Patel, H. N., Busam, K. J., Kutzner, H., Cho, K.-H., Aiba, S., Bröcker, E.-B., LeBoit, P. E., et al. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa050092 · Cited by 2,747 · see citing works
A role for sunlight in skin-cancer – UV-induced p53 mutations in squamous-cell carcinoma
Brash, D. E., Rudolph, J. A., Simon, J. A., Lin, A., McKenna, G. J., Baden, H. P., Halperin, A. J., & Pontén, J. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.22.10124 · Cited by 1,959 · see citing works
The Protective Role of Melanin Against UV Damage in Human Skin <sup>†</sup>
Brenner, M., & Hearing, V. J. (2008) · Photochemistry and Photobiology · doi:10.1111/j.1751-1097.2007.00226.x · Cited by 1,741 · see citing works
High frequency of BRAF mutations in nevi
Pollock, P. M., Harper, U. L., Hansen, K. S., Yudt, L. M., Stark, M., Robbins, C. M., Moses, T. Y., Hostetter, G., Wagner, U., Kakareka, J., et al. (2003) · Nature Genetics · doi:10.1038/ng1054 · Cited by 1,730 · see citing works
A comprehensive catalogue of somatic mutations from a human cancer genome
Pleasance, E. D., Cheetham, R. K., Stephens, P. J., McBride, D. J., Humphray, S. J., Greenman, C. D., Varela, I., Lin, M.-L., Ordóñez, G. R., Bignell, G. R., et al. (2010) · Nature · doi:10.1038/nature08658 · Cited by 1,696 · see citing works
Mutation hotspots due to sunlight in the p53 gene of nonmelanoma skin cancers.
Ziegler, A., Leffell, D. J., Kunala, S., Sharma, H. W., Gailani, M. R., Simon, J. A., Halperin, A. J., Baden, H. P., Shapiro, P. E., & Bale, A. E. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.9.4216 · Cited by 739 · see citing works
Mouret, S., Baudouin, C., Charveron, M., Favier, A., Cadet, J., & Douki, T. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0604213103 · Cited by 684 · see citing works
Self-citationChildhood sun exposure as a risk factor for melanoma: a systematic review of epidemiologic studies
Whiteman, D. C., Whiteman, C. A., & Green, A. C. (2001) · Cancer Causes & Control · doi:10.1023/a:1008980919928 · Cited by 633 · see citing works
Wavelength dependence of oxidative DNA damage induced by UV and visible light
Kielbassa, C. (1997) · Carcinogenesis · doi:10.1093/carcin/18.4.811 · Cited by 616 · see citing works
Ultraviolet A and melanoma: A review
Wang, S. Q., Setlow, R. B., Berwick, M., Polsky, D., Marghoob, A. A., Kopf, A. W., & Bart, R. S. (2001) · Journal of the American Academy of Dermatology · doi:10.1067/mjd.2001.114594 · Cited by 454 · see citing works
Douki, T., Reynaud-Angelin, A., Cadet, J., & Sage, E. (2003) · Biochemistry · doi:10.1021/bi034593c · Cited by 452 · see citing works
Self-citationUV-induced DNA damage and melanin content in human skin differing in racial/ethnic origin
Tadokoro, T., Kobayashi, N., Zmudzka, B. Z., Ito, S., Wakamatsu, K., Yamaguchi, Y., Korossy, K. S., Miller, S. A., Beer, J. Z., & Hearing, V. J. (2003) · The FASEB Journal · doi:10.1096/fj.02-0865fje · Cited by 378 · see citing works
Cellular mechanisms regulating human melanogenesis
Park, H., Kosmadaki, M., Yaar, M., & Gilchrest, B. A. (2009) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-009-8703-8 · Cited by 374 · see citing works
Douki, T., & Cadet, J. (2001) · Biochemistry · doi:10.1021/bi0022543 · Cited by 337 · see citing works
Self-citationAction spectrum for DMA damage in alfalfa lowers predicted impact of ozone depletion
Quaite, F. E., Sutherland, B. M., & Sutherland, J. C. (1992) · Nature · doi:10.1038/358576a0 · Cited by 314 · see citing works
You, Y.-H., Lee, D.-H., Yoon, J.-H., Nakajima, S., Yasui, A., & Pfeifer, G. P. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m107696200 · Cited by 314 · see citing works
Freeman, S. E., Hacham, H., Gange, R. W., Maytum, D. J., Sutherland, J. C., & Sutherland, B. M. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.14.5605 · Cited by 311 · see citing works
Ultraviolet B but not Ultraviolet A Radiation Initiates Melanoma
De Fabo, E. C., Noonan, F. P., Fears, T., & Merlino, G. (2004) · Cancer Research · doi:10.1158/0008-5472.can-04-1454 · Cited by 279 · see citing works
Frelon, S., Douki, T., Ravanat, J.-L., Pouget, J.-P., Tornabene, C., & Cadet, J. (2000) · Chemical Research in Toxicology · doi:10.1021/tx000085h · Cited by 271 · see citing works
Self-citationUltraviolet radiation and melanoma: a systematic review and analysis of reported sequence variants
Hocker, T. L. H., & Tsao, H. (2007) · Human Mutation · doi:10.1002/humu.20481 · Cited by 255 · see citing works
Distribution and Repair of Bipyrimidine Photoproducts in Solar UV-irradiated Mammalian Cells
Perdiz, D., Gróf, P., Mezzina, M., Nikaido, O., Moustacchi, E., & Sage, E. (2000) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)61437-7 · Cited by 248 · see citing works
Kuluncsics, Z., Perdiz, D., Brulay, E., Muel, B., & Sage, E. (1999) · Journal of Photochemistry and Photobiology B: Biology · doi:10.1016/s1011-1344(99)00034-2 · Cited by 239 · see citing works
Douki, T., Court, M., Sauvaigo, S., Odin, F., & Cadet, J. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.16.11678 · Cited by 239 · see citing works
Self-citationPowerful Skin Cancer Protection by a CPD-Photolyase Transgene
Jans, J., Schul, W., Sert, Y.-G., Rijksen, Y., Rebel, H., Eker, A. P. M., Nakajima, S., van Steeg, H., de Gruijl, F. R., Yasui, A., et al. (2005) · Current Biology · doi:10.1016/j.cub.2005.01.001 · Cited by 227 · see citing works
Redox Regulation in Human Melanocytes and Melanoma
Meyskens, F. L., Farmer, P. J., & Fruehauf, J. P. (2001) · Pigment Cell Research · doi:10.1034/j.1600-0749.2001.140303.x · Cited by 225 · see citing works
Absorption spectrum of DNA for wavelengths greater than 300 nm
Sutherland, J. C., & Griffin, K. P. (1981) · Radiation Research · doi:10.2307/3575456 · Cited by 214 · see citing works
Sensitized formation of oxidatively generated damage to cellular DNA by UVA radiation
Cadet, J., Douki, T., Ravanat, J.-L., & Di Mascio, P. (2009) · Photochemical & Photobiological Sciences · doi:10.1039/b905343n · Cited by 213 · see citing works
Self-citationYamaguchi, Y., Takahashi, K., Zmudzka, B. Z., Kornhauser, A., Miller, S. A., Tadokoro, T., Berens, W., Beer, J. Z., Hearing, V. J., Yamaguchi, Y., et al. (2006) · The FASEB Journal · doi:10.1096/fj.06-5725fje · Cited by 205 · see citing works
Microarray expression profiling in melanoma reveals a BRAF mutation signature
Pavey, S. J., Johansson, P. A., Packer, L., Taylor, J. M., Stark, M. S., Pollock, P. M., Walker, G. J., Boyle, G. M., Harper, U. L., Cozzi, S., et al. (2004) · Oncogene · doi:10.1038/sj.onc.1207563 · Cited by 190 · see citing works
α‐MSH activates immediate defense responses to UV‐induced oxidative stress in human melanocytes
Song, X., Mosby, N., Yang, J., Xu, A., Abdel‐Malek, Z., & Kadekaro, A. L. (2009) · Pigment Cell & Melanoma Research · doi:10.1111/j.1755-148x.2009.00615.x · Cited by 163 · see citing works
UVA Generates Pyrimidine Dimers in DNA Directly
Jiang, Y. D., Rabbi, M., Kim, M., Ke, C., Lee, W., Clark, R. L., Mieczkowski, P. A., & Marszałek, P. E. (2009) · Biophysical Journal · doi:10.1016/j.bpj.2008.10.030 · Cited by 162 · see citing works
Courdavault, S., Baudouin, C., Charveron, M., Canguilhem, B., Favier, A., Cadet, J., & Douki, T. (2005) · DNA Repair · doi:10.1016/j.dnarep.2005.05.001 · Cited by 156 · see citing works
Self-citationJiveskog, S., Ragnarsson-Olding, B., Platz, A., & Ringborg, U. (1998) · Journal of Investigative Dermatology · doi:10.1046/j.1523-1747.1998.00376.x · Cited by 155 · see citing works
UVA-induced cyclobutane pyrimidine dimers in DNA: a direct photochemical mechanism?
Mouret, S., Philippe, C., Gracia-Chantegrel, J., Banyasz, A., Karpati, S., Markovitsi, D., & Douki, T. (2010) · Organic & Biomolecular Chemistry · doi:10.1039/b924712b · Cited by 149 · see citing works
Self-citationRepair of UV Light-Induced DNA Damage and Risk of Cutaneous Malignant Melanoma
Wei, Q., Lee, J. E., Gershenwald, J. E., Ross, M. I., Mansfield, P. F., Strom, S. S., Wang, L., Guo, Z., Qiao, Y., Amos, C. I., et al. (2003) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/95.4.308 · Cited by 148 · see citing works
Courdavault, S., Baudouin, C., Charveron, M., Favier, A., Cadet, J., & Douki, T. (2004) · Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis · doi:10.1016/j.mrfmmm.2004.07.011 · Cited by 145 · see citing works
Self-citationYohn, J. J., Norris, D. A., Yrastorza, D. G., Buno, I. J., Leff, J. A., Hake, S. S., & Repine, J. E. (1991) · Journal of Investigative Dermatology · doi:10.1111/1523-1747.ep12480983 · Cited by 139 · see citing works
Melanocytes are deficient in repair of oxidative DNA damage and UV-induced photoproducts
Wang, H.-T., Choi, B., & Tang, M.-S. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1005244107 · Cited by 119 · see citing works
Young, A. R., Potten, C. S., Nikaido, O., Parsons, P. G., Boenders, J., Ramsden, J. M., & Chadwick, C. A. (1998) · Journal of Investigative Dermatology · doi:10.1046/j.1523-1747.1998.00435.x · Cited by 117 · see citing works
Evidence of ultraviolet type mutations in xeroderma pigmentosum melanomas
Wang, Y., DiGiovanna, J. J., Stern, J. B., Hornyak, T. J., Raffeld, M. A., Khan, S. G., Oh, K., Hollander, M. C., Dennis, P. A., & Kraemer, K. H. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0812401106 · Cited by 101 · see citing works
Role of UV in Cutaneous Melanoma†
Maddodi, N., & Setaluri, V. (2008) · Photochemistry and Photobiology · doi:10.1111/j.1751-1097.2007.00283.x · Cited by 100 · see citing works
Cotter, M. A., Thomas, J., Cassidy, P., Robinette, K., Jenkins, N., Florell, S. R., Leachman, S., Samlowski, W. E., & Grossman, D. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-1187 · Cited by 92 · see citing works
Coelho, S. G., & Hearing, V. J. (2010) · Pigment Cell & Melanoma Research · doi:10.1111/j.1755-148x.2009.00656.x · Cited by 91 · see citing works
The Insulated SolarFenton Hybrid Process: Fundamental Investigations
Sagawe, G., Lehnard, A., Lübber, M., & Bahnemann, D. W. (2001) · Helvetica Chimica Acta · doi:10.1002/1522-2675(20011219)84:12 · Cited by 78 · see citing works
Ultraviolet A does not induce melanomas in a <i>Xiphophorus</i> hybrid fish model
Mitchell, D. L., Fernandez, A. A., Nairn, R. S., Garcia, R., Paniker, L., Trono, D., Thames, H. D., & Gimenez-Conti, I. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1000324107 · Cited by 75 · see citing works
Melanin content of cultured human melanocytes and UV-induced cytotoxicity
Leeuw, S. M. D., Smit, N. P. M., Veldhoven, M. V., Pennings, E. J. M., Pavel, S., Simons, J. W. I. M., & Schothorst, A. A. (2001) · Journal of Photochemistry and Photobiology B Biology · doi:10.1016/s1011-1344(01)00168-3 · Cited by 68 · see citing works
Larsson, P., Andersson, E., Johansson, U., Öllinger, K. M., & Rosdahl, I. K. (2005) · Experimental Dermatology · doi:10.1111/j.0906-6705.2005.00238.x · Cited by 65 · see citing works
Gidanian, S., Mentelle, M., Meyskens, F. L., & Farmer, P. J. (2008) · Photochemistry and Photobiology · doi:10.1111/j.1751-1097.2008.00309.x · Cited by 63 · see citing works
Spectral Regions Contributing to Melanoma: A Personal View
Setlow, R. B. (1999) · Journal of Investigative Dermatology Symposium Proceedings · doi:10.1038/sj.jidsp.5640180 · Cited by 58 · see citing works
Melanoma, long wavelength ultraviolet and sunscreens: Controversies and potential resolutions
Lund, L. P., & Timmins, G. S. (2007) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2007.01.007 · Cited by 48 · see citing works
Individual Photosensitivity of Human Skin and UVA-Induced Pyrimidine Dimers in DNA
Mouret, S., Leccia, M. ‐., Bourrain, J. ‐., Douki, T., & Béani, J. (2011) · Journal of Investigative Dermatology · doi:10.1038/jid.2011.47 · Cited by 43 · see citing works
Self-citationMarrot, L., Belaïdi, J.-P., Jones, C., Perez, P., & Meunier, J. (2004) · Photochemistry and Photobiology · doi:10.1562/2004-10-13-ra-343 · Cited by 40 · see citing works
Schothorst, A. A., Evers, L. M., Noz, K. C., Filon, R., & van Zeeland, A. A. (1990) · Journal of Investigative Dermatology · doi:10.1111/1523-1747.ep12475443 · Cited by 33 · see citing works
Hill, H. Z., Hill, G. J., Cieszka, K., Plonka, P. M., Mitchell, D. L., MEYENHOFER, M. F., Xin, P., & Boissy, R. E. (1997) · Photochemistry and Photobiology · doi:10.1111/j.1751-1097.1997.tb07958.x · Cited by 32 · see citing works
THE UV ACTION SPECTRA FOR THE CLONE‐FORMING ABILITY OF CULTURED HUMAN MELANOCYTES AND KERATINOCYTES
Leeuw, S. M. D., Janssen, S., Simons, J. W. I. M., et al. (1994) · Photochemistry and Photobiology · doi:10.1111/j.1751-1097.1994.tb05060.x · Cited by 26 · see citing works
Marrot, L., Belaïdi, J.-P., Jones, C., Perez, P., & Meunier, J. (2005) · Photochemistry and Photobiology · doi:10.1562/2004-10-13-ra-343.1 · Cited by 19 · see citing works
Cutaneous Melanoma: How Does Ultraviolet Light Contribute to Melanocyte Transformation?
Walker, G. J. (2008) · Future Oncology · doi:10.2217/14796694.4.6.841 · Cited by 16 · see citing works
Mouret, S., Sauvaigo, S., Peinnequin, A., Favier, A. E., Béani, J., & Leccia, M. ‐. (2005) · Experimental Dermatology · doi:10.1111/j.0906-6705.2005.00296.x · Cited by 16 · see citing works
Self-citationKowalczuk, C. I., Priestner, M. C., Baller, C. A., et al. (2001) · International Journal of Radiation Biology · doi:10.1080/09553000110062521 · Cited by 13 · see citing works
Leeuw, S. M. D., Simons, J. W. I. M., Vermeer, B., et al. (1995) · Journal of Investigative Dermatology · doi:10.1111/1523-1747.ep12318107 · Cited by 8 · see citing works
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- Authors
- Mouret, S., Forestier, A., & Douki, T.
- Affiliations
- Université Joseph Fourier (FR)
- Corresponding author
- Douki, Thierry
- Venue
- Photochemical & Photobiological Sciences
- Published
- 2012-11
- Volume
- 11
- Issue
- 1
- Pages
- 155-162
- ISSN
- 1474-905X (ISSN-L)
- 1474-9092
- OpenAlex
- W2045626886
- Cited by
- 94
- References
- 62
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 8 · 2023: 3 · 2022: 7 · 2021: 5 · 2020: 5 · 2019: 7 · 2018: 5 · 2017: 7 · 2016: 7 · 2015: 4 · 2014: 13 · 2013: 8 · 2012: 7
- FWCI
- 3.62
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Photochemical & Photobiological Sciences (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Agence Nationale de la Recherche (ANR-07-PCVI-0004)
- 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
- UVA, DNA damage, melanocytes, keratinocytes, melanoma, melanomagenesis, 8-oxo-7,8-dihydroguanine, oxidative DNA damage, strand breaks, Fpg-sensitive sites, pyrimidine dimers, oxidative stress, melanin, mutation spectrum, skin cancer
- MeSH terms
- Chromatography, High Pressure Liquid, DNA, DNA Damage, Humans, Melanocytes, Pyrimidine Dimers, Ultraviolet Rays, Comet Assay, Tandem Mass Spectrometry
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