DNA modifications by the ù-3 lipid peroxidation-derived mutagen 4-Oxo-2-hexenal in vitro and their analysis in mouse and human DNA

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, Yun Shan Li, Hiroshi Kasai

研究成果: Article

10 引文 斯高帕斯(Scopus)

摘要

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-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.

原文English
頁(從 - 到)630-636
頁數7
期刊Chemical Research in Toxicology
23
發行號3
DOIs
出版狀態Published - 2010 三月 15

All Science Journal Classification (ASJC) codes

  • Toxicology

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    Kawai, K., Chou, P. H., Matsuda, T., Inoue, M., Aaltonen, K., Savela, K., Takahashi, Y., Nakamura, H., Kimura, T., Watanabe, T., Sawa, R., Dobashi, K., Li, Y. S., & Kasai, H. (2010). DNA modifications by the ù-3 lipid peroxidation-derived mutagen 4-Oxo-2-hexenal in vitro and their analysis in mouse and human DNA. Chemical Research in Toxicology, 23(3), 630-636. https://doi.org/10.1021/tx9003819