A comparison of the effects of diverse mutagens at the lacZ transgene and Dlb-1 locus in vivo

Transgenic assays permit the detection of mutations in any tissue, whereas endogenous mutations can be measured in very few. For this reason compariso ns between these loci when both can be measured in the same cells are of co nsiderable interest. Previous comparisons have been inconsistent: usually t hese loci have responded alike, however, in some cases the endogenous locus has been more sensitive and at other times the transgenic locus has been m ore sensitive. Here we report a comparison of the lacZ transgene of the Mut a(TM)Mouse and the endogenous Dlb-1 gene in the epithelium of the small int estine after acute exposure to seven mutagens, Benzo[a]pyrene, 5-bromo-2'-d eoxyuridine, methyl methane sulphonate, ethyl methane sulphonate, N-ethyl-N -nitrosourea, mitomycin C and N-methyl-N-nitrosourea were all given by gava ge to F-1 (MutaMouse x SWR) mice. Mutations were quantified 2 weeks after t he end of treatment. The data shows that all of the agents induced similar mutant frequencies at the Dlb-1 locus and at the lacZ transgene, The acute treatments generally produced only modest increases in mutant frequency at both loci. The higher background frequency observed at the lacZ transgene r educes the ability of the transgenic assay to detect the same absolute incr ease in mutant frequency.