Identification of 4-oxo-2-hexenal and other direct mutagens formed in model lipid peroxidation reactions as dGuo adducts.
We searched for mutagens that react with 2'-deoxyguanosine (dGuo) in model systems of lipid peroxidation. To autoxidation systems of methyl linoleate (model of omega-6 fat), methyl alpha-linolenate (MLN) (model of omega-3 fat), and commercial salad oil, dGuo was added. The reaction mixtures were analyzed by HPLC. Six adducts were detected, and their structures were determined by 1H and 13C NMR, UV, and mass spectra and by comparison with synthetic authentic samples. The mutagens that reacted with dGuo to form these adducts were proposed as glyoxal, glyoxylic acid, ethylglyoxal, and 4-oxo-2-hexenal (4-OHE). The formation of 8-hydroxy-dGuo, an oxidized product of dGuo, was also detected in the model reaction mixtures. Among them, glyoxal and glyoxylic acid are known mutagens, while ethylglyoxal and 4-OHE, produced from MLN, have not been reported as mutagens thus far. We confirmed the mutagenic activity of 4-OHE with Salmonella strains, TA100 and TA104, without S9 mix. These compounds may be involved in lipid peroxide-related cancers.
Maekawa
Muneyuki
M
Department of Environmental Oncology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health (UOEH), 1-1, Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan.
Kawai
Kazuaki
K
Takahashi
Yoshikazu
Y
Nakamura
Hikaru
H
Watanabe
Takumi
T
Sawa
Ryuichi
R
Hachisuka
Kenji
K
Kasai
Hiroshi
H
D000447:Aldehydes / Q000032:analysis / Q000737:chemistry* / Q000633:toxicity; D003849:Deoxyguanosine / Q000032:analysis / Q000737:chemistry*; D006038:Glyoxylates / Q000032:analysis / Q000737:chemistry; D006427:Hemin; D008041:Linoleic Acids; D008042:Linolenic Acids; D015227:Lipid Peroxidation; D008954:Models, Biological; D009152:Mutagenicity Tests; D009153:Mutagens / Q000032:analysis / Q000737:chemistry* / Q000633:toxicity; D010938:Plant Oils; D011765:Pyruvaldehyde / Q000031:analogs & derivatives / Q000032:analysis / Q000737:chemistry; D012475:Salmonella / Q000187:drug effects / Q000235:genetics
C506591:4-oxo-(E)-2-hexenal; D000447:Aldehydes; D006038:Glyoxylates; D008041:Linoleic Acids; D008042:Linolenic Acids; D009153:Mutagens; D010938:Plant Oils; C047376:methyl linolenate; C005575:methyl linoleate; C022138:ethylglyoxal; D011765:Pyruvaldehyde; D006427:Hemin; D003849:Deoxyguanosine; C031150:glyoxylic acid