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
