Exocyclic deoxyadenosine adducts of 1,2,3,4-diepoxybutane: synthesis, structural elucidation, and mechanistic studies.

ABSTRACT: 1,2,3,4-Diepoxybutane (DEB) is considered the ultimate carcinogenic metabolite of 1,3-butadiene, an important industrial chemical and environmental pollutant present in urban air. Although it preferentially modifies guanine within DNA, DEB induces a large number of A --> T transversions, suggesting that it forms strongly mispairing lesions at adenine nucleobases. We now report the discovery of three potentially mispairing exocyclic adenine lesions of DEB: N(6),N(6)-(2,3-dihydroxybutan-1,4-diyl)-2'-deoxyadenosine (compound 2), 1,N(6)-(2-hydroxy-3-hydroxymethylpropan-1,3-diyl)-2'-deoxyadenosine (compound 3), and 1,N(6)-(1-hydroxymethyl-2-hydroxypropan-1,3-diyl)-2'-deoxyadenosine (compound 4). The structures and stereochemistry of the novel DEB-dA adducts were determined by a combination of U

SUBMITTER: Seneviratne U 

PROVIDER: S-EPMC2807914 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature