title: The mutagenic effect of ultraviolet-A1 on human skin demonstrated by sequencing the p53 gene in single keratinocytes.
abstract: BACKGROUND
  Sun exposure is accepted as the major risk factor for developing skin cancer, the most common cancer in the western world. Ultraviolet-B (UV-B) radiation is considered the causative agent, but recently several findings suggest a role also for ultraviolet-A (UV-A) radiation. Repeated suberythemal doses of ultraviolet-A1 (UV-A1) on healthy human skin induce an increase of p53 immunoreactive cells in epidermis, which may indicate cell cycle arrest and/or occurrence of p53 mutations.
  
  
  METHODS
  We have investigated the possible mutagenic effect of UV-A1 on skin by sequencing exons 4-11 and adjacent intron sequence of the p53 gene in immunoreactive single cells from three healthy individuals. Previously unexposed buttock skin was irradiated three times a week for 2 weeks with physiological fluences (40 J/cm2) of UV-A1. Punch biopsies were taken before and at different time-points after the exposure, and from these single p53 immunoreactive cells were isolated by using laser-assisted microdissection.
  
  
  RESULTS
  Three mutations--all being indicative of oxidative damage and most likely related to UV-A exposure--were found among the 37 single cells from exposed skin, whereas no mutations were found in the 22 single cells taken before exposure.
  
  
  CONCLUSIONS
  The findings indicate a mutagenic effect of low-dose UV-A1 on healthy human skin, which further demonstrates the importance of considering UV-A when taking protective measures against skin cancer.
authors.affiliation: Department of Biotechnology, Royal Institute of Technology (KTH), SCFAB, S-106 91 Stockholm, Sweden.
authors.forename: Asa E
authors.initials: AE
authors.lastname: Persson
authors.forename: Desiree W
authors.initials: DW
authors.lastname: Edström
authors.forename: Helena
authors.initials: H
authors.lastname: Bäckvall
authors.forename: Joakim
authors.initials: J
authors.lastname: Lundeberg
authors.forename: Fredrik
authors.initials: F
authors.lastname: Pontén
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Ros
authors.forename: Cecilia
authors.initials: C
authors.lastname: Williams
mesh_terms: D017931:DNA Primers; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D015603:Keratinocytes / Q000528:radiation effects*; D009154:Mutation; D016133:Polymerase Chain Reaction; D014466:Ultraviolet Rays
chemical_list: D017931:DNA Primers