Reaction of glyoxal with 2'-deoxyguanosine, 2'-deoxyadenosine, 2'-deoxycytidine, cytidine, thymidine, and calf thymus DNA: identification of DNA adducts.
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.
Olsen
Raymond
R
National Institute of Occupational Health, P.O. Box 8149 Dep., N-0033 Oslo, Norway.
Molander
Paal
P
Øvrebø
Steinar
S
Ellingsen
Dag G
DG
Thorud
Syvert
S
Thomassen
Yngvar
Y
Lundanes
Elsa
E
Greibrokk
Tyge
T
Backman
Josefin
J
Sjöholm
Rainer
R
Kronberg
Leif
L
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
D018736:DNA Adducts; D003839:Deoxyadenosines; D003841:Deoxycytidine; D006037:Glyoxal; D003562:Cytidine; D004247:DNA; D003849:Deoxyguanosine; D013936:Thymidine