title: Cell surface expression of melanocortin-1 receptor on HaCaT keratinocytes and alpha-melanocortin stimulation do not affect the formation and repair of UVB-induced DNA photoproducts.
abstract: Ultraviolet (UV) exposure induces an up-regulation of melanocortin-1 receptor (MC1R) expression in human skin and the alpha-melanocyte-stimulating hormone (alpha-MSH) may reduce UVB-induced DNA damage in normal human melanocytes. Using high-performance liquid chromatography coupled to tandem mass spectrometry, we investigated the formation and repair of DNA lesions in UVB-irradiated HaCaT cells stably transfected with the wild type MC1R gene (HaCaT-MC1R). Similar levels of 8 bipyrimidine photoproducts including cyclobutane pyrimidine dimers (CPDs) (T<>T, T<>C, C<>T), (6-4) photoproducts ((6-4)PPs) (TT-(6-4)PPs, TC-(6-4)PPs) and their Dewar valence isomers together with 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) were found to be generated in both non-transfected and HaCaT-MC1R cells after UVB exposure. Time-course studies of DNA photoproduct yields indicated that the DNA repair ability depended upon radiation doses. It was shown that (6-4)PPs were removed from the DNA of UVB-irradiated cells much more efficiently than CPDs. The repair efficiency of 8-oxodGuo, CPDs and (6-4)PPs was relatively similar in both cell lines and was not modified by stimulation with alpha-MSH before UVB-exposure. In conclusion, cell surface-enforced expression of MC1Rs on HaCaT keratinocytes and alpha-MSH stimulation do not affect the formation of UVB-induced DNA photoproducts and their subsequent repair.
authors.affiliation: UMR CNRS 5247 (IBMM), Université Montpellier I - Faculté de Pharmacie, 15 Av. Charles Flahault BP 14 491, 34093, Montpellier Cedex 5, and Department of Dermatology, Groupe Hospitalo-Universitaire Caremeau, Nimes, France.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Garcin
authors.forename: Thierry
authors.initials: T
authors.lastname: Douki
authors.forename: Pierre-Emmanuel
authors.initials: PE
authors.lastname: Stoebner
authors.forename: Joëlle
authors.initials: J
authors.lastname: Guesnet
authors.forename: Anne
authors.initials: A
authors.lastname: Guezennec
authors.forename: Jean
authors.initials: J
authors.lastname: Martinez
authors.forename: Jean
authors.initials: J
authors.lastname: Cadet
authors.forename: Laurent
authors.initials: L
authors.lastname: Meunier
mesh_terms: D002460:Cell Line; D004249:DNA Damage / Q000528:radiation effects; D004260:DNA Repair / Q000502:physiology*; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism*; D011740:Pyrimidine Dimers / Q000737:chemistry / Q000235:genetics / Q000528:radiation effects; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics / Q000378:metabolism*; D014466:Ultraviolet Rays / Q000009:adverse effects*; D000521:alpha-MSH / Q000494:pharmacology*
chemical_list: D011740:Pyrimidine Dimers; D044102:Receptor, Melanocortin, Type 1; D000521:alpha-MSH