Genotoxicity of lipid oxidation compounds

Lipid peroxidation, the oxidative degradation of membrane lipids by reactive oxygen species generates a large variety of breakdown products such as alkanes, aldehydes, ketones, alcohols, furans and others. Due to their reactivity aldehydes (alkanals, 2-alkenals, 2,4-alkadienals, 4-hydroxyalkenals) received a lot of attention, in particular because they can diffuse from the site of formation and interact with proteins and nucleic acids thus acting as second toxic messengers. The major aldehydic peroxidation product of membrane lipids is 4-hydroxynonenal (HNE). Since HNE and other 4-hydroxyalkenals are strong alkylating agents they have therefore been considered to be the biologically most important peroxidation products. Although initially research focused on the toxicological potential of these compounds it is now well known that they play also a crucial role in cell signaling under physiological and pathophysiological conditions. Thus, it is obvious that the biological effects will be determined by the intracellular concentrations which can trigger adaptation, DNA damage and cell death. This review will not cover all these aspects but will concentrate on the genotoxic properties of selected lipid oxidation products important in the context of pathophysiological developments together with a chapter on epigenetic modifications.