Mutational spectra in the lacl gene in skin from XXXX -treated and untreated @entity19 .

@entity3653 @entity19 @entity1324 @entity54202 @entity106 @entity2704 @entity13009 @entity105
@entity19 carrying the bacterial lacl gene in a lambda shuttle vector were used to isolate and characterize background and @entity3653 ( @entity106 )-induced mutations in skin. Adult male @entity19 were treated once topically with either @entity106 or @entity1324 or were left untreated. Seven days later, @entity106 treatment had significantly increased the mutant frequency in the skin (mean +/- SEM, 36 +/- 3 x 10(-5)) versus in vehicle-treated (6.4 +/- 1.2 x 10(-5)) and untreated @entity19 (7.1 x 1.0 x 10(-5)). At least 10 mutants from each of three @entity106 -treated and three untreated @entity19 were selected for DNA sequence analysis. In each case, the entire 1080-bp target gene was sequenced. Base-pair substitutions predominated (86 of 96 mutations), although frameshift and deletion mutations were also detected. Twelve percent of the mutants carried more than one mutation. In controls, the mutations were predominantly @entity54202 transitions (26 of 42), and no @entity13009 transversions were recovered. In contrast, in the @entity106 -treated @entity19 , @entity13009 transversions represented 42% of the mutations (23 of 54) and @entity54202 transitions accounted for only 11%. The @entity13009 transversions occurred mostly at 5'-CA sites. This class of mutation has been recovered frequently in ras genes from @entity106 -treated @entity19 and probably represents an early event in @entity105 ( @entity2704 et al., Proc Natl Acad Sci USA 89:6398-6402, 1992). Our present results are consistent with the types of DNA damage induced by @entity106 . The observation of different mutant frequencies and spectra in treated and control @entity19 demonstrates the utility of this approach in the study of mutagenesis in vivo.
