DNA Modifications by the ω-3 Lipid Peroxidation-Derived Mutagen 4-Oxo-2-hexenal in Vitro and Their Analysis in Mouse and Human DNA

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• 作者：Kazuaki Kawai ; Pei-Hsin Chou ; Tomonari Matsuda ; Masaaki Inoue ; Kaisa Aaltonen ; Kirsti Savela ; Yoshikazu Takahashi ; Hikaru Nakamura ; Tomoyuki Kimura ; Takumi Watanabe ; Ryuichi Sawa ; Kazuyuki Dobashi ; Yu
• 刊名：Chemical Research in Toxicology
• 出版年：2010
• 出版时间：March 15, 2010
• 年：2010
• 卷：23
• 期：3
• 页码：630-636
• 全文大小：232K
• 年卷期：v.23,no.3(March 15, 2010)
• ISSN：1520-5010

文摘

4-Oxo-2-hexenal (4-OHE), which forms a 2′-deoxyguanosine (dG) adduct in a model lipid peroxidation system, is mutagenic in the Ames test. It is generated by the oxidation of ω-3 fatty acids and is commonly found in dietary fats, such as fish oil, perilla oil, rapeseed oil, and soybean oil. 4-OHE also forms adducts with 2′-deoxyadenosine (dA), 2′-deoxycytidine (dC), and 5-methyl-2′-deoxycytidine (5-Me-dC) in DNA. In this study, we characterized the structures of these adducts in detail. We measured the amounts of 4-OHE−DNA adducts in mouse organs by LC/MS/MS, after 4-OHE was orally administered to mice. The 4-OHE−dA, 4-OHE−dC, 4-OHE−dG, and 4-OHE−5-Me-dC adducts were detected in stomach and intestinal DNA in the range of 0.25−43.71/10⁸ bases. After the 4-OHE administration, the amounts of these DNA adducts decreased gradually over 7 days. We also detected 4-OHE−dC in human lung DNA, in the range of 2.6−5.9/10⁹ bases. No difference in the 4-OHE adduct levels was detected between smokers and nonsmokers. Our results suggest that 4-OHE−DNA adducts are formed by endogenous as well as environmental lipid peroxides.