In vivo detection of a novel endogenous etheno-DNA adduct derived from arachidonic acid and the effects of antioxidants on its formation

体内检测源自花生四烯酸的新型内源性乙烯-DNA加合物以及抗氧化剂对其形成的影响

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作者:Ying Fu #, Raghu G Nath #, Marcin Dyba #, Idalia M Cruz, Sharanya R Pondicherry, Aileen Fernandez, Casey L Schultz, Peiying Yang, Jishen Pan, Dhimant Desai, Jacek Krzeminski, Shantu Amin, Plamen P Christov, Yukihiko Hara, Fung-Lung Chung

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

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