N(2)-(1-Carboxyethyl)deoxyguanosine, a nonenzymatic glycation adduct of DNA, induces single-strand breaks and increases mutation frequencies

Biochem Biophys Res Commun. 1999 Oct 22;264(2):544-9. doi: 10.1006/bbrc.1999.1528.


N(2)-(1-Carboxyethyl)deoxyguanosine (CEdG) is a major nonenzymatic glycation product of DNA. The effect of CEdG modification, which was specifically prepared by incubation with dihydroxyacetone, on plasmid DNA topology was evaluated by gel electrophoresis. A time-dependent decrease of supercoiled plasmid-DNA was observed in parallel to the increase of CEdG adducts; the half-life time of the supercoiled plasmid-DNA was estimated to be approximately 16-18 h. CEdG-modified plasmid DNA showed a 25-fold reduced transformation efficiency. When modified DNA was used to transform Escherichia coli cells, a 6-fold increase in mutation frequency was determined by measuring loss of alpha-complementation. For the mutator strain BMH71-18mutS, an 8-fold increase in mutation frequency was observed. Although the exact mechanism of DNA damage is unclear, the occurrence of spontaneous depurination is likely. These findings suggest that a defined DNA glycation reaction can lead to DNA damage in vivo.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA Adducts / pharmacology*
  • DNA Damage*
  • DNA Repair / genetics
  • DNA, Single-Stranded / chemistry
  • DNA, Single-Stranded / drug effects*
  • DNA, Single-Stranded / metabolism
  • DNA, Superhelical / chemistry
  • DNA, Superhelical / drug effects*
  • DNA, Superhelical / metabolism
  • Electrophoresis, Agar Gel
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Glucose / chemistry
  • Half-Life
  • Mutation
  • Oxidation-Reduction
  • Plasmids / chemistry


  • DNA Adducts
  • DNA, Single-Stranded
  • DNA, Superhelical
  • Glucose