Carcinogen-specific Mutational Pattern in the p53 Gene in Ultraviolet B Radiation-induced Squamous Cell Carcinomas of Mouse Skin1

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- The details of the experimental procedure used for tumor induction by chronic UVB radiation in mice of the indicated strains have been reported elsewhere (7, 8). In brief, SKH-1 hr mice were exposed twice per week to gradually increasing doses from 1 kJ/cm2 to 6 kJ/cm2 starting at Wk 4 of age and lasting until sacrifice of the animals. Pap- illomas were isolated between 22 and 26 wk and carcinomas between 32 and 36 wk after the start of treatment. Chronic irradiation of shaved SENCAR, BALB/c, and C3H/He mice was carried out 3 times/wk with 2.88 kJ/cm2 from FS40 sun lamps. Exposures were continued until sacrifice of the animals. Tumors (SCCs) were isolated from SENCAR and BALB/c mice between 18 and 24 wk and from C3H/He mice between 26 and 36 wk after start of treatment. Two of the tumors from SENCAR mice were induced by single UVB radiation (8.64 J/cm2). strand conformation polymorphism analysis and sequencing. Base sub stitutions were found in seven tumors (20%). All mutations occurred at dipyrimidine sequences; most frequent were C I single base and CC —¿TTtandem transitions suggesting the involvement of UV radia tion in the genSuiter, Paul T.esis 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 pS3 mutations. Introduction