Epoxidation of trans-4-hydroxy-2-nonenal by fatty acid hydroperoxides and hydrogen peroxide.
In this study, we reported that fatty acid hydroperoxides and hydrogen peroxide are capable of epoxidizing 4-hydroxy-2-nonenal, a lipid peroxidation product, to the mutagenic epoxide. The evidence of its formation is provided (i) by trapping with [8-3H]deoxyadenosine for the formation of 7-(1',2'-dihydroxyheptyl)-1,N6-ethenodeoxyadenosine as a pair of diastereomers, (ii) by derivatization with (2,4-dinitrophenyl)hydrazine in acidic methanol, and (iii) by comparing its 1H-nuclear magnetic resonance and mass spectra to those of the authentic standard. After incubating 4-hydroxy-2-nonenal with 9- or 13-linoleic acid hydroperoxide at 37 degrees C for 24 h, the epoxide was produced in 13.4% or 12.5% yield, and with hydrogen peroxide, the yield was 21.5%. In the presence of fatty acid (linoleic acid, gamma-linolenic acid, or arachidonic acid) and lipoxygenase, the epoxide of 4-hydroxy-2-nonenal was formed in 15.3%, 7.2%, or 6.2% yield, respectively. The xanthine/xanthine oxidase/superoxide dismutase system generated the epoxide in 1.2% yield. These yields are estimated on the basis of a standard curve obtained from reactions of deoxyadenosine and epoxide. These results show that 4-hydroxy-2-nonenal is epoxidized by biological oxidants, suggesting a plausible endogenous pathway for the in vivo formation of etheno adducts.
Chen
H J
HJ
Division of Chemical Carcinogenesis, American Health Foundation, Valhalla, New York 10595, USA.
Chung
F L
FL
D000447:Aldehydes / Q000737:chemistry* / Q000633:toxicity; D001711:Biotransformation; D004852:Epoxy Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D005231:Fatty Acids, Unsaturated / Q000737:chemistry / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008054:Lipid Peroxides / Q000737:chemistry / Q000494:pharmacology*; D016877:Oxidants / Q000633:toxicity
D000447:Aldehydes; D004852:Epoxy Compounds; D005231:Fatty Acids, Unsaturated; D008054:Lipid Peroxides; D016877:Oxidants; D006861:Hydrogen Peroxide; C027576:4-hydroxy-2-nonenal