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The butadiene metabolite, 1,2:3,4‐diepoxybutane, induces micronuclei but is only weakly mutagenic at lacI in the Big Blue® Rat2 lacI transgenic cell line
Author(s) -
Saranko Christopher J.,
Recio Leslie
Publication year - 1998
Publication title -
environmental and molecular mutagenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 87
eISSN - 1098-2280
pISSN - 0893-6692
DOI - 10.1002/(sici)1098-2280(1998)31:1<32::aid-em5>3.0.co;2-d
Subject(s) - micronucleus test , microbiology and biotechnology , mutagen , micronucleus , genotoxicity , chemistry , mutant , mutagenesis , carcinogen , transgene , biology , toxicity , biochemistry , gene , organic chemistry
1,3‐Butadiene (BD) is a genotoxic carcinogen that is bioactivated to at least two mutagenic metabolites, 1,2‐epoxybutene (EB) and 1,2:3,4‐diepoxybutane (DEB). We investigated the mutagenicity and induction of micronuclei by DEB in vitro in Rat2 lambda/ lacI transgenic fibroblasts (Big Blue® Rat2 cells, Stratagene, LaJolla, CA). Assays for mutagenicity and micronuclei induction were carried out at concentrations of 0, 2, 5, or 10 μM DEB for 24 hours. Exposure of cells to these concentrations of DEB resulted in approximately 100, 50, and 10% survival, respectively, compared with media controls. In independent replicate experiments, no statistically significant increase in lacI mutant frequency was observed in Rat2 cells at any of the DEB exposure concentrations when compared tomedia or solvent controls. However, regressionanalyses indicated a trend toward increasing mutant frequency with increasing DEB exposure concentration. Experiments to examine the induction of micronuclei by DEB revealed a concentration‐dependent increase in micronuclei in Rat2 cells following exposure to DEB. These results indicate that DEB induces micronuclei in the absence of detectable gene mutation at lacI in Big Blue Rat2 cells. The induction ofmicronuclei but only weak mutagenicity at the lacI transgene is likely due to the poor recovery of deletions using this lambda shuttle vector system, demonstrating the need to investigate multiple endpoints of genotoxicity when considering the mutational activity of a compound. Environ. Mol. Mutagen. 31:32–40, 1998. © 1998 Wiley‐Liss, Inc.