Characterization of the adducts formed in the reactions of glycidamide with thymidine and cytidine

Chem Res Toxicol. 2004 Dec;17(12):1652-8. doi: 10.1021/tx049823i.

Abstract

Glycidamide (GA) is a mutagenic epoxide metabolite of acrylamide (AM), a high production chemical with many industrial uses. Moreover, recent findings have shown that AM is formed in starchy foods cooked at high temperatures. This has refocused the attention on this chemical and its metabolite and on their possible mutagenicity and carcinogenicity. In this study, we have reacted GA with cytidine and thymidine in aqueous-buffered solutions. The adducts from the nucleosides have been isolated by reversed phase HPLC and characterized by their UV absorbance and 1H and 13C NMR spectroscopic and mass spectrometric features. The reaction with thymidine yielded one adduct, N3-(2-carbamoyl-2-hydroxyethyl)thymidine (N3-GA-dThd), while the reaction with cytidine yielded three adducts. Two adducts were identified as a diastereomeric pair of N3-(2-carboxy-2-hydroxyethyl)cytidine (N3-GA-Cyd-1 and N3-GA-Cyd-2). The third adduct from the cytidine reaction was identified as N3-(2-carboxy-2-hydroxyethyl)uridine (N3-GA-Urd).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromatography, High Pressure Liquid
  • Cytidine / chemistry*
  • Cytidine / metabolism
  • DNA Adducts / chemistry*
  • DNA Adducts / isolation & purification
  • Epoxy Compounds / chemistry*
  • Epoxy Compounds / metabolism
  • Epoxy Compounds / toxicity
  • Mutagens / chemistry*
  • Mutagens / toxicity
  • Spectrometry, Mass, Electrospray Ionization
  • Thymidine / chemistry*
  • Thymidine / metabolism

Substances

  • DNA Adducts
  • Epoxy Compounds
  • Mutagens
  • Cytidine
  • glycidamide
  • Thymidine