P53 MUTATIONS IN CUTANEOUS LESIONS INDUCED IN THE HAIRLESS MOUSE BY ASOLAR ULTRAVIOLET-LIGHT SIMULATOR

We investigated skin lesions induced in hairless SKH:HR1 mice by chron ic exposure to a solar ultraviolet light (UV) simulator for alteration s 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 (hype rplasias), 25 precancerous skin lesions (keratoacanthomas), and 25 mal ignant skin lesions (squamous cell carcinomas; SCC) by polymerase chai n reaction-single-strand conformation polymorphism analysis. Most of t he mutations occurred at dipyrimidine sequences located on the nontran scribed strand; the most frequent modifications were C-->T transitions (77%) and CC-->TT tandem mutations (5%); the latter are considered th e UV fingerprint. p53 mutations were detected in 3% of the hyperplasia s, 12% of the keratoacanthomas, and 52% of the SCCs. Hence, the high f requency of p53 mutations in SCCs compared with keratoacanthomas induc ed by a solar UV simulator suggested that, in our study, p53 mutations probably occurred as a late event in the skin carcinogenesis progress ion of SCC. Interestingly, the level of CC-->TT tandem mutations in th e 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 hai rless mouse skin tumors induced by a solar UV simulator confirmed the major role of UVB-induced DNA damage in skin carcinogenesis and sugges ted that UVA plays a minor role in bringing about p53 alterations. Mol . Carcinog. 22: 167-174, 1998. (C) 1998 Wiley-Liss, Inc.