title: Reaction of glyoxal with 2'-deoxyguanosine, 2'-deoxyadenosine, 2'-deoxycytidine, cytidine, thymidine, and calf thymus DNA: identification of DNA adducts.
abstract: Glyoxal (ethanedial) is an increasingly used industrial chemical that has been found to be mutagenic in bacteria and mammalian cells. In this study, the reactions of glyoxal with 2'-deoxyguanosine, 2'-deoxyadenosine, 2'-deoxycytidine, cytidine, thymidine, and calf thymus DNA have been studied in aqueous buffered solutions. The nucleoside adducts were isolated by reversed-phase liquid chromatography and characterized by their UV absorbance and 1H and 13C NMR spectroscopic and mass spectrometric features. The reaction with 2'-deoxyguanosine gave one adduct, the previously known 3-(2'-deoxy-beta-D-erythro-pentofuranosyl)-5,6,7-trihydro-6,7-dihydroxyimidazo[1,2-a]purine-9-one adduct. The reaction of 2'-deoxyadenosine with glyoxal resulted in the formation of a previously not reported N6-(hydroxyacetyl)-2'-deoxyadenosine adduct. In the reaction of glyoxal with 2'-deoxycytidine and cytidine at neutral conditions and 37 degrees C, 5-hydroxyacetyl pyrimidine derivatives were obtained. When the cytidine reaction was performed at pH 4.5 and 50 degrees C, the 5-hydroxyacetyl derivative of uridine was formed through deamination of cytidine-glyoxal. Adducts in the thymidine reaction could not be detected. In the reaction of glyoxal with calf thymus DNA, the 2'-deoxyguanosine-glyoxal and 2'-deoxyadenosine-glyoxal adducts were obtained, the former being the major adduct.
authors.affiliation: National Institute of Occupational Health, P.O. Box 8149 Dep., N-0033 Oslo, Norway.
authors.forename: Raymond
authors.initials: R
authors.lastname: Olsen
authors.forename: Paal
authors.initials: P
authors.lastname: Molander
authors.forename: Steinar
authors.initials: S
authors.lastname: Øvrebø
authors.forename: Dag G
authors.initials: DG
authors.lastname: Ellingsen
authors.forename: Syvert
authors.initials: S
authors.lastname: Thorud
authors.forename: Yngvar
authors.initials: Y
authors.lastname: Thomassen
authors.forename: Elsa
authors.initials: E
authors.lastname: Lundanes
authors.forename: Tyge
authors.initials: T
authors.lastname: Greibrokk
authors.forename: Josefin
authors.initials: J
authors.lastname: Backman
authors.forename: Rainer
authors.initials: R
authors.lastname: Sjöholm
authors.forename: Leif
authors.initials: L
authors.lastname: Kronberg
mesh_terms: D003562:Cytidine / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D018736:DNA Adducts / Q000032:analysis*; D003839:Deoxyadenosines / Q000378:metabolism; D003841:Deoxycytidine / Q000378:metabolism; D003849:Deoxyguanosine / Q000378:metabolism; D006037:Glyoxal / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D013936:Thymidine / Q000378:metabolism
chemical_list: D018736:DNA Adducts; D003839:Deoxyadenosines; D003841:Deoxycytidine; D006037:Glyoxal; D003562:Cytidine; D004247:DNA; D003849:Deoxyguanosine; D013936:Thymidine