TY - JOUR
T1 - Quantitation by liquid chromatography-nanoelectrospray ionization-high resolution tandem mass spectrometry of DNA adducts derived from methyl glyoxal and carboxyethylating agents in leukocytes of smokers and non-smokers
AU - Cheng, Guang
AU - Reisinger, Sarah A.
AU - Shields, Peter G.
AU - Hatsukami, Dorothy K.
AU - Balbo, Silvia
AU - Hecht, Stephen S.
N1 - Publisher Copyright:
© 2020 Elsevier B.V.
PY - 2020/8/25
Y1 - 2020/8/25
N2 - A liquid chromatograpy-nanoelectrospray ionization-high resolution tandem mass spectrometry (LC–NSI–HRMS/MS) method was developed for quantitation of the DNA adducts 7-(2′-carboxyethyl)guanine (7-2′-CEG) and N2-(1′-carboxyethyl)guanine (N2-1′-CEG), as their methyl esters, in human leukocyte DNA from smokers and non-smokers. 7-2′-CEG has been previously identified in all human liver samples analyzed and is formed from an unknown carboxyethylating agent while N2-1′-CEG is formed from the advanced glycation endproduct methyl glyoxal. The method was applied for the analysis of these two DNA adducts in leukocyte DNA from 20 smokers and 20 non-smokers, in part to test the hypothesis that 7-2′-CEG could be formed by endogenous nitrosation, as previously observed in rats treated with nitrosodihydrouracil and nitrite. Levels of 7-2′-CEG (mean ± S.D.) were 0.6 ± 0.2 pmol/μmol dG in smokers and 0.5 ± 0.2 pmol/μmol dG in non-smokers, while those of N2-1′-CEG were 4.5 ± 1.9 pmol/μmol dG in smokers and 4.6 ± 2 pmol/μmol dG in non-smokers. These results did not support our hypothesis that endogenous nitrosation of dihydrouracil in smokers leads to higher levels of 7-2′-CEG in leukocyte DNA than in non-smokers. However the study provides the first data on levels of these DNA adducts in human leukocyte DNA, and the LC–NSI–HRMS/MS method developed for their quantitation could be important for future studies of DNA damage by methyl glyoxal.
AB - A liquid chromatograpy-nanoelectrospray ionization-high resolution tandem mass spectrometry (LC–NSI–HRMS/MS) method was developed for quantitation of the DNA adducts 7-(2′-carboxyethyl)guanine (7-2′-CEG) and N2-(1′-carboxyethyl)guanine (N2-1′-CEG), as their methyl esters, in human leukocyte DNA from smokers and non-smokers. 7-2′-CEG has been previously identified in all human liver samples analyzed and is formed from an unknown carboxyethylating agent while N2-1′-CEG is formed from the advanced glycation endproduct methyl glyoxal. The method was applied for the analysis of these two DNA adducts in leukocyte DNA from 20 smokers and 20 non-smokers, in part to test the hypothesis that 7-2′-CEG could be formed by endogenous nitrosation, as previously observed in rats treated with nitrosodihydrouracil and nitrite. Levels of 7-2′-CEG (mean ± S.D.) were 0.6 ± 0.2 pmol/μmol dG in smokers and 0.5 ± 0.2 pmol/μmol dG in non-smokers, while those of N2-1′-CEG were 4.5 ± 1.9 pmol/μmol dG in smokers and 4.6 ± 2 pmol/μmol dG in non-smokers. These results did not support our hypothesis that endogenous nitrosation of dihydrouracil in smokers leads to higher levels of 7-2′-CEG in leukocyte DNA than in non-smokers. However the study provides the first data on levels of these DNA adducts in human leukocyte DNA, and the LC–NSI–HRMS/MS method developed for their quantitation could be important for future studies of DNA damage by methyl glyoxal.
KW - 7-(2′-carboxyethyl)guanine
KW - Advanced glycation end products
KW - Endogenous nitrosation
KW - Liquid chromatograpy-nanoelectrospray ionization-high resolution tandem mass spectrometry
KW - Methyl glyoxal
KW - N-(1′-carboxyethyl)guanine
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U2 - 10.1016/j.cbi.2020.109140
DO - 10.1016/j.cbi.2020.109140
M3 - Article
C2 - 32442416
AN - SCOPUS:85086151432
SN - 0009-2797
VL - 327
JO - Chemico-Biological Interactions
JF - Chemico-Biological Interactions
M1 - 109140
ER -