1. Reaction of Glyoxal with 2-Deoxyguanosine, 2-Deoxyadenosine, 2-Deoxycytidine, Cytidine, Thymidine, and Calf Thymus DNA: Identification of DNA Adducts
- Author
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Olsen, R., Molander, P., Ovrebo, S., Ellingsen, D. G., Thorud, S., Thomassen, Y., Lundanes, E., Greibrokk, T., Backman, J., Sjoholm, R., and Kronberg, L.
- 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-β-
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 °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.- Published
- 2005