Carcinogen-specific mutational pattern in the p53 gene in ultraviolet B radiation-induced squamous cell carcinomas of mouse skin.

Abstract

We have examined 35 epidermal tumors induced in mice of four different strains by chronic exposure to ultraviolet B radiation for the presence of aberrations in the p53 tumor suppressor gene. Polymerase chain reaction products from p53 exons 5 to 8 were screened by single-strand conformation polymorphism analysis and sequencing. Base substitutions were found in seven tumors (20%). All mutations occurred at dipyrimidine sequences; most frequent were C-->T single base and CC-->TT tandem transitions suggesting the involvement of UV radiation in the genesis of the mutations. Three base substitutions were located at codon 148, and all dipyrimidine-derived mutations occurred at sites where the sequence is present in the nontranscribed DNA strand, indicating some site and strand specificity of the ultraviolet B-induced p53 mutations.