title: Oxidative DNA damage and cardiovascular disease.
abstract: Reactive oxygen species can directly cause covalent modifications to DNA. Alternatively, they can initiate the formation of lipid hydroperoxides, which undergo homolytic decomposition to the alpha,beta-unsaturated aldehyde genotoxins, 4-oxo-2-nonenal, 4,5-epoxy-2(E)-decenal, and 4-hydroxy-2-nonenal through two quite separate pathways. One pathway involves a complex rearrangement of the alkoxy radical derived from the lipid hydroperoxide. The other pathway involves the intermediate formation of 4-hydroperoxy-2-nonenal. Lipid hydroperoxides can also be derived from the action of lipoxygenases and cyclooxygenases on polyunsaturated fatty acids. 4,5-Epoxy-2(E)-decenal forms etheno-2'-deoxyadenosine adduct with DNA, a mutagenic lesion observed in human tissue DNA samples. Several new ethano- and etheno-DNA adducts have been identified from the reaction of 4-oxo-2-nonenal with DNA. Malondialdehyde, another genotoxic bifunctional electrophile, forms a propano adduct with 2'-deoxyguanosine (M1G-dR) rather than an etheno adduct. Very little is known about the consequences of lipid hydroperoxide-mediated DNA damage in cardiovascular diseases. This should prove to be an important area for future research.
authors.affiliation: Center for Cancer Pharmacology, 1254 BRB II/III, 421 Curie Bvd., University of Pennsylvania, Philadelphia, PA 19104-6160, USA.
authors.forename: S H
authors.initials: SH
authors.lastname: Lee
authors.forename: I A
authors.initials: IA
authors.lastname: Blair
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004249:DNA Damage; D005544:Forecasting; D006801:Humans; D008054:Lipid Peroxides / Q000009:adverse effects / Q000378:metabolism; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000009:adverse effects / Q000378:metabolism
chemical_list: D008054:Lipid Peroxides; D017382:Reactive Oxygen Species; D004247:DNA