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-β-<SCP>d</SCP>-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 °C, 5-hydroxyacetyl pyrimidine derivatives were obtained. When the cytidine reaction was performed at pH 4.5 and 50 °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.