Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Seidl, H; Kreimer-Erlacher, H; Bäck, B; Soyer, HP; Höfler, G; Kerl, H; Wolf, P.
Ultraviolet exposure as the main initiator of p53 mutations in basal cell carcinomas from psoralen and ultraviolet A-treated patients with psoriasis.
J Invest Dermatol. 2001; 117(2):365-370
Doi: 10.1046/j.0022-202x.2001.01413.x
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- Führende Autor*innen der Med Uni Graz
- Seidl Hannes
- Wolf Peter
- Co-Autor*innen der Med Uni Graz
- Höfler Gerald
- Kerl Helmut
- Soyer Hans Peter
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- Abstract:
- Basal cell carcinoma, the most frequent skin cancer in humans, is often linked to chronic sun exposure. In psoralen and ultraviolet A-treated psoriatic patients, basal cell carcinomas may occur even more frequently; however, the exact etiology and mechanisms of tumorigenesis in psoriatic patients are unclear because psoralen and ultraviolet A is not only a carcinogen but also an immunosuppressor and because psoralen and ultraviolet A-treated psoriatic patients often have other (co)carcinogenic risk factors (e.g, therapeutic exposure to ultraviolet B, X-ray radiation, arsenic, tar, and/or chemotherapeutic agents such as methotrexate). In this study, we analyzed the DNA of 13 basal cell carcinomas from five psoralen and ultraviolet A-treated psoriatic patients for mutations of the p53 tumor suppressor gene. DNA sequencing revealed a total of 11 mis-sense, two non-sense, and four silent mutations in seven of the 13 basal cell carcinomas (54%). Of the 13 total mis-sense or non-sense mutations, 12 (92%) occurred at dipyrimidine sites and nine (69%) were of the ultraviolet fingerprint type (eight C-->T transitions and one CC-->TT transition). Three of the C-->T transitions occurred at dipyrimidine sites opposite a 5'-TpG sequence (a potential psoralen-binding site and target for psoralen and ultraviolet A mutagenesis). Thus, whether these mutations were induced by ultraviolet or psoralen and ultraviolet A was not clear. In addition, two other mutations (15%) occurred at 5'-TpG sites, one (8%) occurred at a 5'-TpA site (the most frequent site of psoralen binding and mutagenesis in cell and murine studies), and one (8%) involved a G-->T transversion. These results suggest that (i) the major initiator of p53 mutations in basal cell carcinoma in psoralen and ultraviolet A-treated psoriasis patients is environmental and/or therapeutic ultraviolet(B) exposure, and that (ii) psoralen and ultraviolet A itself causes only a smaller portion of p53 mutations in psoralen and ultraviolet A-associated basal cell carcinomas.
- Find related publications in this database (using NLM MeSH Indexing)
- Adult -
- Aged -
- Carcinoma, Basal Cell - epidemiology
- Female -
- Ficusin - adverse effects
- Humans -
- Incidence -
- Male -
- Middle Aged -
- PUVA Therapy - adverse effects
- Photosensitizing Agents - adverse effects
- Point Mutation - drug effects
- Polymorphism, Single-Stranded Conformational -
- Psoriasis - complications
- Skin Neoplasms - epidemiology
- Tumor Suppressor Protein p53 - genetics
- Ultraviolet Rays - adverse effects
- Find related publications in this database (Keywords)
- carcinogenesis
- mutagenesis
- skin cancer