INCREASED FREQUENCY OF MUTATIONS AT A-T BASE-PAIRS IN THE BONE-MARROW OF B6C3F1 LACL TRANSGENIC MICE EXPOSED TO 1,3-BUTADIENE

We have examined the spectra of mutations in a collection of 74 lacl mutants isolated from the bone marrow of B6C3F1 lad 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 ED induces an increased frequency of in vivo mutation at A:T base pairs in the bone marrow of B6C3F1 loci transgenic mice. (C) 1995 Wiley-liss, Inc.