linoleic-acid-hydroperoxide and ferric-chloride

Lipid peroxides are suggested to be related to the occurrence of a variety of diseases including cancer and atherosclerosis. We examined whether lipid peroxides cause oxidative damage to DNA in intact cells. Linoleic acid hydroperoxide (LOOH) and ferric chloride were used at concentrations at which separate treatment had no effect on the formation of 8-oxo-2'-deoxyguanosine (8-oxodG) in DNA or the survival rate of cultured human diploid fibroblasts, TIG-7. The amount of 8-oxodG in the cellular DNA increased significantly when TIG-7 cells were treated concurrently with LOOH and ferric chloride. In a LOOH concentration-dependent manner 8-oxodG was formed. However, no significant induction of the activities of superoxide dismutases, catalase, or glutathione peroxidase was observed under these conditions. The formation of 8-oxodG by lipid hydroperoxides seems to be due to the generation of reactive species other than superoxide radicals and hydrogen peroxide. These results indicate that some species formed during the reaction of lipid hydroperoxides with ferric ion can cause oxidative damage to DNA.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Catalase; Cell Line; Cell Survival; Chlorides; Deoxyguanosine; Diploidy; DNA; DNA Damage; Dose-Response Relationship, Drug; Enzyme Induction; Ferric Compounds; Fibroblasts; Glutathione Peroxidase; Humans; Ions; Linoleic Acids; Lipid Peroxidation; Lipid Peroxides; Oxidative Stress; Reactive Oxygen Species; Superoxide Dismutase; Superoxides

Topics: Catalysis; Chlorides; Cysteine; Ferric Compounds; Hydrogen-Ion Concentration; Iron; Linoleic Acids; Lipid Peroxides; Nitroblue Tetrazolium; Oxygen Consumption; Superoxide Dismutase

1. The degradation of linoleic acid hydroperoxide by cysteine and FeCl3 resulted in formation of a number of oxygenated fatty acids, among which isomeric epoxyoxooctadecenoic and epoxyhydroxyoctadecenoic acids were major products. Pure isomeric hydroperoxides, either 13-L(S)-hydroperoxy-cis-9,trans-11-octadecadienoic acid or 9-D(S)-hydroperoxy-trans-10,cis-12-octadecadienoic acid, were transformed into either 12,13-epoxides or 9,10-epoxides, respectively. 2. From 13-L(S)-hydroperoxy-cis-9,trans-11-octadecadienoic acid, the epoxides were identified as trans-12,13-epoxy-9-oxo-trans-10-octadecenoic acid, trans-12,13-epoxy-9-hydroxy-trans-10-octadecenoic acid, cis-12,13-epoxy-9-oxo-trans-10-octadecenoic acid, trans-12,13-epoxy-erythro-11-hydroxy-cis(trans)-9-octadecenoic acid and trans-12,13-epoxy-threo-11-hydroxy-cis(trans)-9-octadecenoic acid. 3. The 12,13-epoxides were found to be optically active, indicating that the chiral center of the 13-L(S)-hydroperoxy carbon was retained. 4. Although many epoxy fatty acids previously have been identified as linoleic acid hydroperoxide products, this study reports a more complete structural analysis of the various epoxides and allows an assessment of the mechanisms of their formation from hydroperoxides.

Topics: Catalysis; Chlorides; Cysteine; Epoxy Compounds; Ethers, Cyclic; Fatty Acids; Ferric Compounds; Gas Chromatography-Mass Spectrometry; Iron; Isomerism; Linoleic Acids; Lipid Peroxides; Magnetic Resonance Spectroscopy

Topics: Catalysis; Chlorides; Cysteine; Ferric Compounds; Gas Chromatography-Mass Spectrometry; Iron; Isomerism; Linoleic Acids; Lipid Peroxides; Magnetic Resonance Spectroscopy; Oleic Acids; Optical Rotation