Shiou-Chi Chang, Uthpala I Seneviratne, Jie Wu, Natalia Tretyakova, John M Essigmann
The adverse effects of the human carcinogen 1,3-butadiene (BD) are believed to be mediated by its DNA-reactive metabolites such as 3,4-epoxybut-1-ene (EB) and 1,2,3,4-diepoxybutane (DEB). The specific DNA adducts responsible for toxic and mutagenic effects of BD, however, have yet to be identified. Recent in vitro polymerase bypass studies of BD-induced adenine (BD-dA) adducts show that DEB-induced N6 ,N6 -DHB-dA (DHB = 2,3-dihydroxybutan-1,4-diyl) and 1,N6 -γ-HMHP-dA (HMHP = 2-hydroxy-3-hydroxymethylpropan-1,3-diyl) adducts block replicative DNA polymerases but are bypassed by human polymerases η and κ, leading to point mutations and deletions...
May 15, 2017: Chemical Research in Toxicology