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The specificity of UVA-induced DNA damage in human melanocytes

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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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  1. Laboratoire «L´esions des Acides Nucl´eiques», SCIB, UMR-E3 CEA/UJFGrenoble 1, INAC, Grenoble, F-38054, France

    Stéphane Mouret, Anne Forestier & Thierry Douki

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  1. Stéphane Mouret
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  2. Anne Forestier
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  3. Thierry Douki
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Correspondence to Thierry Douki.

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Contribution to the themed issue on the biology of UVA.

Electronic supplementary information (ESI) available: Fig. S1: emission spectra of the UV lamps and Table S1: list and expression of studied DNA repair genes.. See DOI: 10.1039/c1pp05185g

§ This work was supported by a grant from the French “Agence National pour la Recherche” (ANR-07-PCVI-0004-01).

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Mouret, S., Forestier, A. & Douki, T. The specificity of UVA-induced DNA damage in human melanocytes. Photochem Photobiol Sci 11, 155–162 (2012). https://doi.org/10.1039/c1pp05185g

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