N2-(1-Carboxyethyl)deoxyguanosine, a Nonenzymatic Glycation Adduct of DNA, Induces Single-Strand Breaks and Increases Mutation Frequencies

doi:10.1006/bbrc.1999.1528

Biochemical and Biophysical Research Communications

Volume 264, Issue 2, 22 October 1999, Pages 544-549

https://doi.org/10.1006/bbrc.1999.1528 Get rights and content

Abstract

N²-(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.

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¹: To whom correspondence should be addressed at Theodor-Boveri-Institut der Universität Würzburg, Physiologische Chemie I, Biozentrum, Am Hubland, 97074 Würzburg, Germany. Fax: +931 888 4150. E-mail: [email protected].

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Regular ArticleN2-(1-Carboxyethyl)deoxyguanosine, a Nonenzymatic Glycation Adduct of DNA, Induces Single-Strand Breaks and Increases Mutation Frequencies

Abstract

Mutat. Res.

Mech. Ageing Dev.

Mutat. Res.

Carbohydr. Res.

Tetrahedron Lett.

Bioorg. Med. Chem. Lett.

Bioorg. Med. Chem. Lett.

Biochim. Biophys. Acta

J. Mol. Biol.

J. Mol. Biol.

Mech. Ageing Dev.

J. Cell. Physiol.

Am. J. Human Genet.

Nature

Nature

Carcinogenesis

Angew. Chem. Int. Ed. Engl.

Annu. Rev. Med.

J. Biol. Chem.

Nature Med.

Regular Article
N²-(1-Carboxyethyl)deoxyguanosine, a Nonenzymatic Glycation Adduct of DNA, Induces Single-Strand Breaks and Increases Mutation Frequencies