4-Oxo-2-hexenal, a mutagen formed by ω-3 fat peroxidation, causes DNA adduct formation in mouse organs

Abstract

To identify mutagens formed in a model reaction of lipid peroxidation, linolenic acid methyl ester and hemin were reacted with dG. As a result, 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 TA 100 and TA 104. After 4-OHE was orally administered to mice, dG*, 4-OHE-dC- and 4-OHE-5-methyl-dC adducts were detected in esophageal, stomach and intestinal DNA. In the vapor phase released from the methyl linolenate-hemin model system, and in the smoke released during the broiling of fish, 4-OHE was detected by GCMS. The 4-OHE seems to be produced by the auto-oxidation of ω-3 polyunsaturated fatty acids. These results provide a warning to workers dealing with ω-3 fats, who may be exposed to this volatile mutagen.