Increased frequency of mutations at A:T base pairs in the bone marrow of B6C3F1 lacI transgenic mice exposed to 1,3-butadiene.
We have examined the spectra of mutations in a collection of 74 lacI mutants isolated from the bone marrow of B6C3F1 lacI transgenic mice exposed to 1,250 ppm 1,3-butadiene (BD). Of the 49 independent mutations analyzed in the present study, 30 of 49 (61%) were point mutations at G:C base pairs, and 10 of 49 (20%) were point mutations at A:T base pairs. The remaining mutations consisted of small deletions and insertions and a single tandem change. An analysis of variance (ANOVA) on the frequency of specific mutations observed in each animal in this mutagenicity experiment [present study; also Sisk SC et al. (1994): Carcinogenesis 15:471-477] indicated that the frequency of point mutations at A:T base pairs is significantly greater (P < 0.05) in BD-exposed mice than in the air controls. In addition, there was a decrease (P < 0.05; Fisher's exact test) in the frequency of G:C-->A:T transitions at 5'-CpG-3' sites in BD-exposed mice (27%) relative to air controls (51%). These data indicate that subchronic exposures to BD induces an increased frequency of in vivo mutation at A:T base pairs in the bone marrow of B6C3F1 lacI transgenic mice.
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Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina 27709, USA.
Meyer
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D000225:Adenine; D000704:Analysis of Variance; D000818:Animals; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics*; D001482:Base Composition; D001483:Base Sequence; D001853:Bone Marrow / Q000187:drug effects* / Q000473:pathology; D002070:Butadienes / Q000633:toxicity*; D004251:DNA Transposable Elements; D029968:Escherichia coli Proteins; D056968:Lac Repressors; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009153:Mutagens / Q000633:toxicity*; D017354:Point Mutation; D012097:Repressor Proteins / Q000096:biosynthesis / Q000235:genetics*; D017384:Sequence Deletion; D013941:Thymine
D001426:Bacterial Proteins; D002070:Butadienes; D004251:DNA Transposable Elements; D029968:Escherichia coli Proteins; D056968:Lac Repressors; D009153:Mutagens; D012097:Repressor Proteins; D000225:Adenine; C031763:1,3-butadiene; D013941:Thymine