p53 mutations in cutaneous lesions induced in the hairless mouse by a solar ultraviolet light simulator.
We investigated skin lesions induced in hairless SKH:HR1 mice by chronic exposure to a solar ultraviolet light (UV) simulator for alterations of the p53 gene in conserved domains. Mutations of exons 5-8 of the p53 gene in skin lesions were screened in 31 benign skin lesions (hyperplasias), 25 precancerous skin lesions (keratoacanthomas), and 25 malignant skin lesions (squamous cell carcinomas; SCC) by polymerase chain reaction-single-strand conformation polymorphism analysis. Most of the mutations occurred at dipyrimidine sequences located on the nontranscribed strand; the most frequent modifications were C-->T transitions (77%) and CC-->TT tandem mutations (5%); the latter are considered the UV fingerprint. p53 mutations were detected in 3% of the hyperplasias, 12% of the keratoacanthomas, and 52% of the SCCs. Hence, the high frequency of p53 mutations in SCCs compared with keratoacanthomas induced by a solar UV simulator suggested that, in our study, p53 mutations probably occurred as a late event in the skin carcinogenesis progression of SCC. Interestingly, the level of CC-->TT tandem mutations in the SCCs (5%) was similar to that found in SCCs induced in hairless mice by UVB alone. p53 protein was also detected in the different types of skin lesions by immunohistochemical analysis. Thus, our data from hairless mouse skin tumors induced by a solar UV simulator confirmed the major role of UVB-induced DNA damage in skin carcinogenesis and suggested that UVA plays a minor role in bringing about p53 alterations.
Laboratory of Molecular Genetics, Centre Nationale de Recherche Scientifique, Institut de Recherche sur le Cancer, Villejuif, France.
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Queille
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Seite
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Tison
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Medaisko
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Drougard
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Fourtanier
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Sarasin
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Daya-Grosjean
D000818:Animals; D005260:Female; D016158:Genes, p53; D051379:Mice; D009154:Mutation; D009381:Neoplasms, Radiation-Induced / Q000235:genetics*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011230:Precancerous Conditions / Q000209:etiology / Q000235:genetics*; D012878:Skin Neoplasms / Q000209:etiology / Q000235:genetics*; D013472:Sunlight / Q000009:adverse effects*; D014466:Ultraviolet Rays / Q000145:classification