Research report (Health Effects Institute)
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Res Rep Health Eff Inst · Mar 2000
1,3-butadiene: cancer, mutations, and adducts. Part II: Roles of two metabolites of 1,3-butadiene in mediating its in vivo genotoxicity.
1,3-Butadiene (BD) is carcinogenic in mice and rats, with mice being more susceptible than rats to its carcinogenic effects. 1,3-Butadiene is mutagenic in the bone marrow and spleen cells of B6C3F1 lacI transgenic mice. The goal of this research was to assess the roles of two BD metabolites, 1,2-epoxy-3-butene (BDO) and 1,2,3,4-diepoxybutane (BDO2), in the mutagenicity and mutational spectrum of the parent compound BD by determining the mutagenicity and mutational spectra of BDO and BDO2 in human and rodent cells in vitro and in vivo. In human TK6 lymphoblastoid cells (TK6 cells), BDO exposure increased the frequency of G. ⋯ Therefore, it is apparent that in mice exposed to BD at carcinogenic levels, BDO and BDO2 act in concert to mediate the range of genotoxic responses. These data demonstrate that certain DNA adducts (guanine or adenine) may be useful biomarkers for BD genetic effects. However, other DNA lesions that can account for BDO2-induced deletions and chromosomal alterations also need to be considered as biomarkers for BD-induced genotoxicity.