TOXI 68 |
| Polyunsaturated fatty acids (PUFAs) can be converted into lipid hydroperoxides either by reactive oxygen species (ROS) or by the action of lipoxygenases (LOXs) and cyclooxygenases (COXs). Lipid hydroperoxides undergo homolytic decomposition into bifunctional electrophiles, which react with DNA bases to form DNA-adducts. Vitamin C-mediated homolytic decomposition of 15(S)-hydroperoxyeicosatetraenoic acid (HPETE) results in the formation of the DNA reactive α,β-unsaturated aldehydic bifunctional electrophiles, 4-hydroperoxy-2(E)-nonenal (HPNE), 4-oxo-2(E)-nonenal (ONE), 4-hydroxy-2(E)-nonenal (HNE), trans-4,5-epoxy-2(E)-decenal (t-EDE), and cis-4,5-epoxy-2(E)-decenal (c-EDE). ONE formed heptanone-etheno-2′-deoxyguanosine (dGuo), heptanone-etheno-2′-deoxyadenosine (dAdo), and heptanone-etheno-2′-deoxycytidine adducts; whereas, HPNE and EDE formed unsubstituted etheno-dGuo and etheno-dAdo adducts. Lower amounts of unsubstituted etheno-dGuo and heptanone-etheno-dGuo were formed from 12(S)-HPETE when compared with 15(S)-HPETE. This suggested that other bifunctional electrophiles were being formed. Adducts produced from the reaction between 12(S)-HPETE and dGuo were characterized by liquid chromatography-tandem mass spectrometry, which allowed these new bifunctional electrophiles to be identified. Supported by NIH grants CA95586 and P30 ES013508. |
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Poster Session and Awards
6:00 PM-10:00 PM, Tuesday, August 21, 2007 BCEC -- 204 A/B, Poster
Sci-Mix
Division of Chemical Toxicology |