title: 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.
authors: Laboratoire Lésions des Acides Nucléiques, SCIB, UMR-E3 CEA/UJF-Grenoble 1, INAC, Grenoble, F-38054, France.
authors: Stéphane
authors: S
authors: Mouret
authors: Anne
authors: A
authors: Forestier
authors: Thierry
authors: T
authors: Douki
mesh_terms: D002851:Chromatography, High Pressure Liquid; D020552:Comet Assay; D004247:DNA / Q000528:radiation effects*; D004249:DNA Damage; D006801:Humans; D008544:Melanocytes / Q000528:radiation effects*; D011740:Pyrimidine Dimers; D053719:Tandem Mass Spectrometry; D014466:Ultraviolet Rays
chemical_list: D011740:Pyrimidine Dimers; D004247:DNA