Structure and potential mutagenicity of new hydantoin products from guanosine and 8-oxo-7,8-dihydroguanine oxidation by transition metals

Cynthia J. Burrows, James G. Muller, Olga Kornyushyna, Wenchen Luo, Victor Duarte, Michael D. Leipold, Sheila S. David

Research output: Contribution to journalArticle

66 Scopus citations

Abstract

In vitro work in this laboratory has identified new DNA lesions resulting from further oxidation of a common biomarker of oxidative damage, 8-oxo-7,8-dihydroguanine (OG). The major product of oxidation of OG in a nucleoside, nucleotide, or single-stranded oligodeoxynucleotide using metal ions that act as one-electron oxidants is the new nucleoside derivative spiroiminodihydantoin (Sp.) In duplex DNA an equilibrating mixture of two isomeric products, guanidinohydantoin (Gh) and iminoallantoin (Ia), is produced. These products are also formed by the overall four-electron oxidation of guanosine by photochemical processes involving O2. DNA template strands containing either Sp or Gh/Ia generally acted as a block to DNA sysnthesis with the Klenow exo- fragment of pol I. However, when nucleotide insertion did occur opposite the lesions, only 2'-deoxyadenosine 5-triphosphate and 2'-deoxyguanine 5-triphosphate were used for primer extension. The Escherichia coli DNA repair enzyme Fpg was able to remove the Sp and Gh/Ia lesion from duplex DNA substrates, although the efficiency was depended on the base opposite the lesion.

Original languageEnglish (US)
Pages (from-to)713-717
Number of pages5
JournalEnvironmental Health Perspectives
Volume110
Issue numberSUPPL. 5
StatePublished - Oct 2002
Externally publishedYes

Keywords

  • DNA damage
  • DNA repair
  • Guanine
  • Oxygen radicals
  • Polymerases
  • Transition metals

ASJC Scopus subject areas

  • Environmental Science(all)
  • Environmental Chemistry
  • Public Health, Environmental and Occupational Health

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    Burrows, C. J., Muller, J. G., Kornyushyna, O., Luo, W., Duarte, V., Leipold, M. D., & David, S. S. (2002). Structure and potential mutagenicity of new hydantoin products from guanosine and 8-oxo-7,8-dihydroguanine oxidation by transition metals. Environmental Health Perspectives, 110(SUPPL. 5), 713-717.