Use of transgenic mice for assessing the mutagenicity of 1,3-butadiene in vivo.

We have examined the mutagenicity of 1,3-butadiene in vivo in transgenic mice constructed with lambda phage shuttle vectors that contain either lacZ or lacI as transgenes. Thus far, we have shown that butadiene is mutagenic to the lung of lacZ mice (CD2F1, 625 ppm butadiene, 6 h/day, 5 days) and to the bone marrow of lacI mice (B6C3F1, 62.5, 625, 1250 ppm butadiene, 6 h/day, 5 days/week, 4 weeks) exposed by inhalation to the same concentrations used previously in bioassays of the carcinogenicity of butadiene. Analysis of the DNA sequences of lacI mutants from the bone marrow of lacI mice demonstrated a shift in the spectrum of mutation from G:C base pairs in the control group to mutation at A:T base pairs in the exposed group. In addition, analysis of DNA sequences of mutations in three animals exposed to butadiene showed evidence of mutant clonal expansion in vivo. These results indicate that butadiene induces mutation in mouse tissues. Analysis of mutations at the level of DNA sequences is useful for examining the relationship between mutation and mutant frequencies in vivo and the spectrum of mutation in transgenic animals after exposures to carcinogens.