Site-specific mutagenicity of stereochemically defined 1, N 2-deoxyguanosine adducts of trans-4-hydroxynonenal in mammalian cells

Priscilla H. Fernandes, Hao Wang, Carmelo J. Rizzo, R. Stephen Lloyd

Research output: Contribution to journalArticlepeer-review

43 Scopus citations


Trans-4-hydroxynonenal (HNE) is a toxic compound produced endogenously during lipid peroxidation. HNE is a potent electrophile that is reactive with both proteins and nucleic acids. HNE preferentially reacts with deoxyguanosine to form four stereoisomeric HNE-deoxyguanosine (HNE-dG) adducts: (6R, 8S, 11R), (6S, 8R, 11S), (6R, 8S, 11S), and (6S, 8R, 11R). These adducts were synthesized into 12-mer oligodeoxynucleotides, inserted into a DNA shuttle vector and evaluated for the ability of each stereoisomer to induce mutagenesis when replicated through mammalian cells. The resultant mutagenicity of these adducts was related to their stereochemistry, in that two of the HNE-dG adducts, (6R, 8S, 11R) and (6S, 8R, 11S), were significantly more mutagenic than the (6R, 8S, 11S) and (6S, 8R, 11R) HNE-dG adducts. These data conclusively demonstrate that HNE-derived DNA adducts can be mutagenic in mammalian cells and their ability to cause mutations is dictated by their stereochemistry.

Original languageEnglish (US)
Pages (from-to)68-74
Number of pages7
JournalEnvironmental and Molecular Mutagenesis
Issue number2
StatePublished - 2003
Externally publishedYes


  • HNE-dG adducts
  • Mutagenicity
  • Stereoisomers
  • Trans-4-hydrononenal

ASJC Scopus subject areas

  • Epidemiology
  • Genetics(clinical)
  • Health, Toxicology and Mutagenesis


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