Formation of adducts in the reaction of glyoxal with 2'-deoxyguanosine and with calf thymus DNA.
The reactions of glyoxal with 2'-deoxyguanosine and calf thymus single- and double-stranded DNA in aqueous buffered solutions at physiological conditions resulted in the formation of two previously undetected adducts in addition to the known reaction product 3-(2'-deoxy-beta-D-erythro-pentofuranosyl)-5,6,7-trihydro-6,7-dihydroxyimidazo[1,2-a]purine-9-one (Gx-dG). The adducts were isolated and purified by reversed-phase liquid chromatography and structurally characterised by UV absorbance, mass spectrometry, (1)H and (13)C NMR spectroscopy. The hitherto unknown adducts were identified as: 5-carboxymethyl-3-(2'-deoxy-beta-D-erythro-pentofuranosyl)-5,6,7-trihydro-6,7-dihydroxyimidazo[1,2-a]purine-9-one (Gx(2)-dG) and N(2)-(carboxymethyl)-9-(2'-deoxy-beta-D-erythro-pentofuranosyl)-purin-6(9H)-one (Gx(1)-dG). Both adducts were shown to arise from Gx-dG. Gx-dG and Gx(2)-dG were found to be unstable and partly transformed to Gx(1)-dG, which is a stable adduct and seems to be the end-product of the glyoxal reaction with 2'-deoxyguanosine. All adducts formed in the reaction of glyoxal with 2'-deoxyguanosine were observed in calf thymus DNA. Also in DNA, Gx(1)-dG was the only stable adduct. The transformation of Gx-dG to Gx(1)-dG seemed to take place in single-stranded DNA and therefore, Gx(1)-dG may be a potentially reliable biomarker for glyoxal exposure and may be involved in the genotoxic properties of the compound.
Pluskota-Karwatka
Donata
D
Faculty of Chemistry, Adam Mickiewicz University, Grunwaldzka 6, 60-780 Poznań, Poland.
Pawłowicz
Agnieszka J
AJ
Tomas
Magdalena
M
Kronberg
Leif
L
D000818:Animals; D004247:DNA / Q000737:chemistry*; D018736:DNA Adducts / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification; D004277:DNA, Single-Stranded; D003849:Deoxyguanosine / Q000737:chemistry*; D006037:Glyoxal / Q000737:chemistry*; D015394:Molecular Structure
D018736:DNA Adducts; D004277:DNA, Single-Stranded; D006037:Glyoxal; D004247:DNA; C427203:calf thymus DNA; D003849:Deoxyguanosine