title: Analysis of 1,N2-ethenoguanine and 5,6,7,9-tetrahydro-7-hydroxy-9-oxoimidazo[1,2-a]purine in DNA treated with 2-chlorooxirane by high performance liquid chromatography/electrospray mass spectrometry and comparison of amounts to other DNA adducts.
abstract: High performance liquid chromatography (HPLC)/electrospray mass spectrometry methods were developed for the analysis of 1,N2-etheno(epsilon)guanine (Gua) and 5,6,7,9-tetrahydro-7-hydroxy-9-oxoidmidazo[1,2-a]purine (HO-ethanoGua) [the cyclized form of N2-(2-oxoethyl)Gua] and its deoxyribose derivative in DNA. Evidence was provided for the formation of the latter adduct in DNA treated with 2-chlorooxirane, the reactive product formed from the carcinogen vinyl chloride. Measured levels of HO-ethanoGua and HO-ethanodeoxyguanosine were similar, although the assay for the deoxyribosyl derivative has some technical advantages. 3,N4-epsilon-Deoxycytidine was also estimated in 2-chlorooxirane-treated DNA using HPLC with fluorescence detection. Levels of all known adducts formed from vinyl chloride have now been estimated in DNA treated with 2-chlorooxirane and vary in the order N7-(2-oxoethyl)Gua >> 1,N6-epsilon-adenine > HO-ethanoGua > N2,3-epsilon-Gua > 3,N4-epsilon-cytosine > 1,N2-epsilon-Gua. Although in vivo adduct levels may not parallel these due to differential stability and rates of repair, analyses of the adducts in DNA treated with 2-chlorooxirane provide a basis for consideration of the biological effects of these adducts.
authors.affiliation: Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
authors.forename: M
authors.initials: M
authors.lastname: Müller
authors.forename: F J
authors.initials: FJ
authors.lastname: Belas
authors.forename: I A
authors.initials: IA
authors.lastname: Blair
authors.forename: F P
authors.initials: FP
authors.lastname: Guengerich
mesh_terms: D000818:Animals; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000187:drug effects*; D018736:DNA Adducts / Q000032:analysis* / Q000138:chemical synthesis; D005027:Ethylene Oxide / Q000031:analogs & derivatives* / Q000494:pharmacology; D005399:Fishes; D008401:Gas Chromatography-Mass Spectrometry; D006151:Guanosine / Q000031:analogs & derivatives* / Q000032:analysis; D007093:Imidazoles / Q000032:analysis*; D008297:Male; D011687:Purines / Q000032:analysis*; D013094:Spermatozoa; D013950:Thymus Gland
chemical_list: D018736:DNA Adducts; D007093:Imidazoles; D011687:Purines; D006151:Guanosine; C085535:5,6,7,9-tetrahydro-7-hydroxy-9-oxoimidazo(1,2-a)purine; C079488:1,N(2)-ethenoguanosine; C015061:chloroethylene oxide; D004247:DNA; D005027:Ethylene Oxide