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.
Document Type: Research Article
Affiliations: 1: Department of Biotechnology, Royal Institute of Technology (KTH), SCFAB, S-106 91 Stockholm, Sweden, 2: Department of Dermatology, Karolinska Hospital, S-171 76 Stockholm, Sweden, and 3: Department of Genetics and Pathology, University Hospital, S-751 85 Uppsala, Sweden
Publication date: December 1, 2002