Conjugation of butadiene diepoxide with glutathione yields DNA adducts in vitro and in vivo.

ABSTRACT: 1,2,3,4-Diepoxybutane (DEB) is reported to be the most potent mutagenic metabolite of 1,3-butadiene, an important industrial chemical and environmental pollutant. DEB is capable of inducing the formation of monoalkylated DNA adducts and DNA-DNA and DNA-protein cross-links. We previously reported that DEB forms a conjugate with glutathione (GSH) and that the conjugate is considerably more mutagenic than several other butadiene-derived epoxides, including DEB, in the base pair tester strain Salmonella typhimurium TA1535 [Cho et al. (2010) Chem. Res. Toxicol. 23, 1544-1546]. In the present study, we determined steady-state kinetic parameters of the conjugation of the three DEB stereoisomers-R,R, S,S, and meso (all formed by butadiene oxidation)-with GSH by six GSH transferases. Only small dif

SUBMITTER: Cho SH 

PROVIDER: S-EPMC3850785 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature