Formation of etheno adducts in reactions of enals via autoxidation.
4-Hydroxy-2-nonenal (HNE) and crotonaldehyde (CA) are alpha,beta-unsaturated aldehydes (enals) produced by lipid peroxidation. Previous studies have shown that enals form tricyclic propano adducts with purine nucleosides. When epoxidized by tert-butyl hydroperoxide, enals yield the more reactive epoxy aldehydes which are capable of modifying adenine and guanine in DNA by forming etheno adducts. The epoxides are considerably more mutagenic and tumorigenic than the parent aldehydes. In this study, we found that, in addition to the propano adducts, etheno adducts are detected upon incubation of enals with deoxyadenosine (dAdo) or deoxyguanosine (dGuo) at 37 degrees C (pH 7.4). When carried out under oxygen-enriched atmosphere, the reaction of HNE with dAdo yielded 1,N6-ethenodeoxyadenosine (1,N6-EdAdo) and 7-(1',2'-dihydroxyheptyl)-1,N6-EdA in 0.03% and 0.48% yield. The reaction with dG gave 0.19% 1,N2-ethenodeoxyguanosine (1,N2-EdGuo) and 0.79% 7-(1',2'-dihydroxyheptyl)-1,N2-EdGuo. In the case of CA, the reaction with dAdo produced 7-(1'-hydroxyethyl)-1,N6-EdAdo in 0.67% yield, while the reaction with dGuo yielded 0.34% 1,N2-EdGuo and 0.97% 7-(1'-hydroxyethyl)-1,N2-EdGuo, respectively. When the above reactions were carried out under nitrogen, yields of etheno adducts were significantly reduced. These results provide evidence for a pathway by which the etheno adducts may be formed by enals via autoxidation.
Chen
H J
HJ
Section of Nucleic Acid Chemistry, American Health Foundation, Valhalla, New York 10595.
Chung
F L
FL
D000447:Aldehydes / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D018736:DNA Adducts / Q000737:chemistry; D003839:Deoxyadenosines / Q000737:chemistry; D003849:Deoxyguanosine / Q000737:chemistry; D004852:Epoxy Compounds / Q000737:chemistry*; D010084:Oxidation-Reduction; D013329:Structure-Activity Relationship
D000447:Aldehydes; D018736:DNA Adducts; D003839:Deoxyadenosines; D004852:Epoxy Compounds; C012796:2-butenal; D003849:Deoxyguanosine; C027576:4-hydroxy-2-nonenal