Molecular dosimetry of n7-guanine adducts in male and female mice exposed to 1,3-butadiene by inhalation

Molecular dosimetry of n7-guanine adducts in male and female mice exposed to 1,3-butadiene by inhalation Public Deposited

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Abstract

1,3-Butadiene (BD) is a well-characterized carcinogen that is both an occupational and environmental hazard and an important industrial chemical widely used in the production of rubber and plastic and is also present in automobile exhaust and cigarette smoke. Upon metabolic activation in vivo, it forms three epoxides that can react with nucleophilic sites in biomolecules: 1,2,3,4-diepoxybutane (DEB), 1,2-epoxy-3-butene (EB), and 3,4-epoxy-1,2-butane-diol (EBD). We characterized the molecular dosimetry of N-7 guanine adduct formation by these metabolites of BD in the liver of male and female B6C3F1 mice exposed to varying levels of BD. The adducts, racemic and meso forms of N-7-(2,3,4-trihydroxy-3-buten-2-yl)guanine (THB-Gua), N-7-(2-hydroxy-3-buten-1-yl)guanine (HB-Gua I), and N-7-(1-hydroxy-3-buten-2-yl)guanine (HB-Gua II) were similar in male and female B6C3F1 mice at all levels where liver tissue was available for both sexes. Thus, no gender differences in adduct formation were noted. The THB-Gua adducts were the most abundant and exhibited a supralinear dose response.

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