title: 4-oxo-2-hexenal, a mutagen formed by omega-3 fat peroxidation: occurrence, detection and adduct formation.
abstract: The purpose of this review is to summarize our recent studies of a novel mutagen, 4-oxo-2-hexenal. To identify the mutagens formed in a model reaction of lipid peroxidation, linolenic acid methyl ester and hemin were reacted with dG. A 4-oxo-2-hexenal-dG adduct (dG*) was identified in the model reaction mixture. The 4-oxo-2-hexenal (4-OHE) showed mutagenic activity in the Salmonella typhimurium strains TA100 and TA104. 4-OHE reacts with DNA to form dG, dC, and 5-methyl-dC(5-Me-dC)-adducts (dG*, dC*, 5-Me-dC*) in vitro. After 4-OHE was orally administered to mice, these adducts were detected in esophageal, stomach and intestinal DNA by liquid chromatography coupled with electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS). We also confirmed the formation of 4-OHE during the heat processing of edible vegetable oil, and during cooking. It was present at an especially high concentration in broiled saury. 4-OHE is probably generated by the oxidation of omega-3 fats. These results provide a warning to humans, who may be exposed to this mutagen. Since 4-OHE induces DNA adduct formation in experimental animal organs, further studies on the carcinogenicity of 4-OHE and the detection of 4-OHE-DNA adducts in human tissue will be required.
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. h-kasai@med.uoeh-u.ac.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kasai
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Kawai
mesh_terms: D000447:Aldehydes / Q000302:isolation & purification* / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D003296:Cooking; D018736:DNA Adducts; D015525:Fatty Acids, Omega-3 / Q000378:metabolism*; D005502:Food; D015386:Hazardous Substances / Q000032:analysis; D006801:Humans; D015227:Lipid Peroxidation; D009153:Mutagens / Q000378:metabolism
chemical_list: C506591:4-oxo-(E)-2-hexenal; D000447:Aldehydes; D018736:DNA Adducts; D015525:Fatty Acids, Omega-3; D015386:Hazardous Substances; D009153:Mutagens