title: DNA modifications by the omega-3 lipid peroxidation-derived mutagen 4-oxo-2-hexenal in vitro and their analysis in mouse and human DNA.
abstract: 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 omega-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 0.25-43.71/10(8) 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 2.6-5.9/10(9) 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.
authors.affiliation: Department of Environmental Oncology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, 1-1, Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Kawai
authors.forename: Pei-Hsin
authors.initials: PH
authors.lastname: Chou
authors.forename: Tomonari
authors.initials: T
authors.lastname: Matsuda
authors.forename: Masaaki
authors.initials: M
authors.lastname: Inoue
authors.forename: Kaisa
authors.initials: K
authors.lastname: Aaltonen
authors.forename: Kirsti
authors.initials: K
authors.lastname: Savela
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Hikaru
authors.initials: H
authors.lastname: Nakamura
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Kimura
authors.forename: Takumi
authors.initials: T
authors.lastname: Watanabe
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Sawa
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Dobashi
authors.forename: Yun-Shan
authors.initials: YS
authors.lastname: Li
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kasai
mesh_terms: D000447:Aldehydes / Q000009:adverse effects*; D000818:Animals; D002417:Cattle; D004247:DNA / Q000378:metabolism; D018736:DNA Adducts / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D006801:Humans; D015227:Lipid Peroxidation; D051379:Mice; D008813:Mice, Inbred ICR; D015394:Molecular Structure; D009153:Mutagens / Q000009:adverse effects*; D009690:Nucleic Acid Conformation
chemical_list: C506591:4-oxo-(E)-2-hexenal; D000447:Aldehydes; D018736:DNA Adducts; D009153:Mutagens; D004247:DNA; C427203:calf thymus DNA