Mutagenesis of the supF gene by stereoisomers of 1,2,3,4-diepoxybutane.

1,2,3,4-diepoxybutane (DEB) is a key metabolite of the important industrial chemical and environmental contaminant, 1,3-butadiene (BD). Although all three optical isomers of DEB, S,S-, R,R-, and meso-DEB, are produced by metabolic processing of BD, S,S-DEB exhibits the most potent genotoxicity and cytotoxicity, followed by R,R- and then meso-DEB. Our previous studies suggested that the observed differences between the biological effects of DEB optical isomers may be structural in their origin. Although S,S- and R,R-DEB produced mainly 1,3-interstrand 1,4-bis-(guan-7-yl)-2,3-butanediol (bis-N7G-BD) cross-links, meso-diepoxide induced equal numbers of intrastrand and interstrand bis-N7G-BD lesions. In the present study, the mutagenicity of the three DEB stereoisomers in the supF gene was investigated. We found that S,S-DEB was the most potent mutagen. Interestingly, mutation specificity and mutant spectra were strongly dependent on DEB stereochemistry. Although A:T to T:A transversions were the major form of mutation observed following treatment with each of the three stereoisomers (35-40%), S,S-DEB induced higher numbers of G:C to A:T transitions, whereas R,R-DEB treatment resulted in a greater frequency of G:C to T:A transversions. Our results are consistent with the stereospecific induction of promutagenic nucleobase adducts other than G-G cross-links by DEB stereoisomers.