TY - JOUR
T1 - DNA modifications by the ù-3 lipid peroxidation-derived mutagen 4-Oxo-2-hexenal in vitro and their analysis in mouse and human DNA
AU - Kawai, Kazuaki
AU - Chou, Pei Hsin
AU - Matsuda, Tomonari
AU - Inoue, Masaaki
AU - Aaltonen, Kaisa
AU - Savela, Kirsti
AU - Takahashi, Yoshikazu
AU - Nakamura, Hikaru
AU - Kimura, Tomoyuki
AU - Watanabe, Takumi
AU - Sawa, Ryuichi
AU - Dobashi, Kazuyuki
AU - Li, Yun Shan
AU - Kasai, Hiroshi
PY - 2010/3/15
Y1 - 2010/3/15
N2 - 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.
AB - 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.
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U2 - 10.1021/tx9003819
DO - 10.1021/tx9003819
M3 - Article
C2 - 20055452
AN - SCOPUS:77949402000
SN - 0893-228X
VL - 23
SP - 630
EP - 636
JO - Chemical Research in Toxicology
JF - Chemical Research in Toxicology
IS - 3
ER -