Identification of octenal-related dA and dC adducts formed by reactions with a hemin-ω-6-fat peroxidation model system

Chem Res Toxicol. 2013 Oct 21;26(10):1554-60. doi: 10.1021/tx400245a. Epub 2013 Oct 1.

Abstract

Deoxynucleosides were reacted in a lipid peroxidation model system, emulsified hemin-ethyl linoleate, and the adducts thus produced were analyzed by HPLC. Substantial amounts of stable adducts were detected in the dA- and dC-reaction mixtures. The structures of the major dA and dC adducts, other than the known 4-oxo-2-nonenal adducts, were determined to be etheno-type adducts, with a C₆ side chain bearing an α-hydroxyl-group. These results suggested that the substance involved in adduct formation is 2,3-epoxyoctanal. This compound showed mutagenicity in Salmonella strains TA 100 and TA 104 without the S-9 mix. In addition, based on the structure of a minor dC adduct, another possibly involved mutagen, 4-oxo-2-octenal, was proposed. These mutagens may be formed during storage and cooking of food, or during digestion, and may be involved in human cancers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehydes / analysis
  • Aldehydes / chemistry*
  • Aldehydes / toxicity
  • Chromatography, High Pressure Liquid*
  • DNA Adducts / analysis*
  • Deoxyadenosines / chemistry
  • Deoxycytidine / chemistry
  • Fatty Acids, Omega-6 / chemistry*
  • Hemin / chemistry*
  • Hemin / metabolism
  • Hydrogen-Ion Concentration
  • Lipid Peroxidation / drug effects
  • Magnetic Resonance Spectroscopy
  • Models, Chemical*
  • Mutagenicity Tests
  • Salmonella / drug effects

Substances

  • 4-oxo-2-nonenal
  • Aldehydes
  • DNA Adducts
  • Deoxyadenosines
  • Fatty Acids, Omega-6
  • Deoxycytidine
  • Hemin
  • 2'-deoxyadenosine
  • caprylic aldehyde