In vivo detection of a novel endogenous etheno-DNA adduct derived from arachidonic acid and the effects of antioxidants on its formation.
Free Radic Biol Med
; 73: 12-20, 2014 Aug.
Article
em En
| MEDLINE
| ID: mdl-24816294
ABSTRACT
Previous studies showed that 7-(1',2'-dihydroxyheptyl)-substituted etheno DNA adducts are products of reactions with the epoxide of (E)-4-hydroxy-2-nonenal, an oxidation product of ω-6 polyunsaturated fatty acids (PUFAs). In this work, we report the detection of 7-(1',2'-dihydroxyheptyl)-1,N(6)-ethenodeoxyadenosine (DHHedA) in rodent and human tissues by two independent methods:
a (32)P-postlabeling/HPLC method and an isotope dilution liquid chromatography-electrospray ionization-tandem mass spectrometry method, demonstrating for the first time that DHHedA is a background DNA lesion in vivo. We showed that DHHedA can be formed upon incubation of arachidonic acid with deoxyadenosine, supporting the notion that ω-6 PUFAs are the endogenous source of DHHedA formation. Because cyclic adducts are derived from the oxidation of PUFAs, we subsequently examined the effects of antioxidants, α-lipoic acid, Polyphenon E, and vitamin E, on the formation of DHHedA and γ-hydroxy-1,N(2)-propanodeoxyguanosine (γ-OHPdG), a widely studied acrolein-derived adduct arising from oxidized PUFAs, in the livers of Long Evans Cinnamon (LEC) rats. LEC rats are afflicted with elevated lipid peroxidation and prone to the development of hepatocellular carcinomas. The results showed that although the survival of LEC rats was increased significantly by α-lipoic acid, none of the antioxidants inhibited the formation of DHHedA, and only Polyphenon E decreased the formation of γ-OHPdG. In contrast, vitamin E caused a significant increase in the formation of both γ-OHPdG and DHHedA in the livers of LEC rats.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Adenosina
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Desoxiadenosinas
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Adutos de DNA
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Desoxiguanosina
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Antioxidantes
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
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Humans
Idioma:
En
Revista:
Free Radic Biol Med
Ano de publicação:
2014
Tipo de documento:
Article