Macromolecular adducts of butadiene.

摘要: Abstract Butadiene (BD) is an important industrial chemical classified as a probable human carcinogen. Marked species differences in susceptibility to the carcinogenic effects of BD have been observed, possibly due its metabolism. In this work, guanine and adenine adducts formed by reactive metabolites vitro were isolated structurally characterized UV spectroscopy, liquid secondary ion mass spectrometry tandem spectrometry, electrospray nuclear magnetic resonance spectroscopy. The prepared reacting purine nucleobases or nucleosides with epoxybutene (EB) diepoxybutane (DEB) followed HPLC separation. reaction (Gua) EB resulted two isomeric products, N 7-(2-hydroxy-3-buten-1-yl) (EB-Gua I) 7-(1-hydroxy-3-buten-2-yl)guanine II). at 3 led formation 3-(2-hydroxy-3-buten-1-yl)adenine (EB-Ade 3-(1-hydroxy-3-buten-2-yl) major adduct DEB was identified 7-(2′,3′,4′-trihydroxybutyl)guanine (DEB-Gua-I). Three products from pH 7 3, 9-(2′,3′,4′-trihydroxybutyl)adenines (DEB-Ade I, II III, respectively). Our results indicate that nucleophilic nitrogens first attack one epoxy groups giving (2′-hydroxy-3′,4′-epoxybutane1-yl) intermediates which can be rapidly hydrolyzed corresponding (2′,3′,4′-trihydroxybutyl) form cross-links DNA proteins. Ade Gua are expected undergo spontaneous depurination repair methylpurine glycosylase therefore may useful biomarkers exposure urine. preliminary data on quantification EB-induced N-terminal valine hemoglobin red blood cells exposed mice rats using modified Edman degradation GC-NI MS investigated. amount EB-N-terminal mouse globin about times greater than explained higher rates and/or limited detoxification mice. Female had amounts males.