These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Characterization of 1,2,3,4-diepoxybutane-2'-deoxyguanosine cross-linking products formed at physiological and nonphysiological conditions.
    Author: Zhang XY, Elfarra AA.
    Journal: Chem Res Toxicol; 2006 Apr; 19(4):547-55. PubMed ID: 16608166.
    Abstract:
    1,2,3,4-Diepoxybutane (DEB), an in vivo metabolite of 1,3-butadiene (BD), is a carcinogen and mutagen. The strong carcinogenicity/mutagenicity of DEB has been attributed to its high DNA reactivity and cross-linking ability. Recently, we have demonstrated that under in vitro physiological conditions (pH 7.4, 37 degrees C), the reaction of DEB with 2'-deoxyguanosine (dG) produced two diastereomeric pairs of the major nucleoside adducts resulting from alkylation at the N1- and N7-positions of dG, that is, 2'-deoxy-1-(2-hydroxy-2-oxiranylethyl)guanosine and 2'-deoxy-7-(2-hydroxy-2-oxiranylethyl)guanosine, respectively [Zhang, X.-Y., and Elfarra, A. A. (2005) Chem. Res. Toxicol. 18, 1316]. As each of these adducts contains an oxirane ring, the abilities of these adducts to form cross-linking products with dG under physiological conditions were investigated. Incubation of the N7 nucleoside adducts and their corresponding guanine product with dG led to formation of 7,7'-(2,3-dihydroxy-1,4-butanediyl)bis[2-amino-1,7-dihydro-6H-purin-6-one] (bis-N7G-BD), a known DEB cross-linking product. Incubation of the N1 nucleoside adducts with dG led to formation of a pair of diastereomers of 2'-deoxy-1-[4-(2-amino-1,7-dihydro-6H-purin-6-on-7-yl)-2,3-dihydroxybutyl]-guanosine (N7G-N1dG-BD), which are novel cross-linking products. Interestingly, the reaction of DEB with dG in glacial acetic acid at 60 degrees C yielded different cross-linking products, which were characterized as 2-amino-9-hydroxymethyl-4-{4-[2-amino-9- or 7-(4-acetyloxy-2,3-dihydroxybutyl)-1,7-dihydro-6H-purin-6-on-7- or 9-yl]-2,3-dihydroxybutyl}-8,9-dihydro-7H-[1,4]oxazepino[4,3,2-gh]purin-8-ol (PA2) and 9,9'-bis(4-acetyloxy-2,3-dihydroxybutyl)-7,7'-(2,3-dihydroxy-1,4-butanediyl)bis[2-amino-1,7-dihydro-6H-purin-6-one] (PA4). Collectively, these results increase our understanding of the chemical reactivity and cross-linking ability of DEB under both physiological and nonphysiological conditions.
    [Abstract] [Full Text] [Related] [New Search]