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

Guang Cheng; Sarah A. Reisinger; Peter G. Shields; Dorothy K. Hatsukami; Silvia Balbo; Stephen S. Hecht

doi:10.1016/j.cbi.2020.109140

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

Guang Cheng, Sarah A. Reisinger, Peter G. Shields, Dorothy K. Hatsukami, Silvia Balbo, Stephen S. Hecht

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

Abstract

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.

Original language	English (US)
Article number	109140
Journal	Chemico-Biological Interactions
Volume	327
DOIs	https://doi.org/10.1016/j.cbi.2020.109140
State	Published - Aug 25 2020

Bibliographical note

Funding Information:
This study was supported by grants CA-138338 from the U.S. National Cancer Institute and CA-203851 and N01 PC-064402 from the U.S. National Cancer Institute and Food and Drug Administration Center for Tobacco Products. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or the Food and Drug Administration. Mass spectrometry was carried out in the Analytical Biochemistry Shared Resource of the Masonic Cancer Center, University of Minnesota , supported in part by Cancer Center Support Grant CA-077598 .

Funding Information:
This study was supported by grants CA-138338 from the U.S. National Cancer Institute and CA-203851 and N01 PC-064402 from the U.S. National Cancer Institute and Food and Drug Administration Center for Tobacco Products. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or the Food and Drug Administration. Mass spectrometry was carried out in the Analytical Biochemistry Shared Resource of the Masonic Cancer Center, University of Minnesota, supported in part by Cancer Center Support Grant CA-077598.

Publisher Copyright:
© 2020 Elsevier B.V.

Keywords

7-(2′-carboxyethyl)guanine
Advanced glycation end products
Endogenous nitrosation
Liquid chromatograpy-nanoelectrospray ionization-high resolution tandem mass spectrometry
Methyl glyoxal
N-(1′-carboxyethyl)guanine

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Cheng, G., Reisinger, S. A., Shields, P. G., Hatsukami, D. K., Balbo, S., & Hecht, S. S. (2020). 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. Chemico-Biological Interactions, 327, [109140]. https://doi.org/10.1016/j.cbi.2020.109140

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. / Cheng, Guang; Reisinger, Sarah A.; Shields, Peter G. et al.

In: Chemico-Biological Interactions, Vol. 327, 109140, 25.08.2020.

Research output: Contribution to journal › Article › peer-review

Cheng, G, Reisinger, SA, Shields, PG, Hatsukami, DK , Balbo, S & Hecht, SS 2020, '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', Chemico-Biological Interactions, vol. 327, 109140. https://doi.org/10.1016/j.cbi.2020.109140

Cheng G, Reisinger SA, Shields PG, Hatsukami DK , Balbo S , Hecht SS. 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. Chemico-Biological Interactions. 2020 Aug 25;327:109140. doi: 10.1016/j.cbi.2020.109140

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title = "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",

abstract = "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.",

keywords = "7-(2′-carboxyethyl)guanine, Advanced glycation end products, Endogenous nitrosation, Liquid chromatograpy-nanoelectrospray ionization-high resolution tandem mass spectrometry, Methyl glyoxal, N-(1′-carboxyethyl)guanine",

author = "Guang Cheng and Reisinger, {Sarah A.} and Shields, {Peter G.} and Hatsukami, {Dorothy K.} and Silvia Balbo and Hecht, {Stephen S.}",

note = "Funding Information: This study was supported by grants CA-138338 from the U.S. National Cancer Institute and CA-203851 and N01 PC-064402 from the U.S. National Cancer Institute and Food and Drug Administration Center for Tobacco Products. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or the Food and Drug Administration. Mass spectrometry was carried out in the Analytical Biochemistry Shared Resource of the Masonic Cancer Center, University of Minnesota , supported in part by Cancer Center Support Grant CA-077598 . Funding Information: This study was supported by grants CA-138338 from the U.S. National Cancer Institute and CA-203851 and N01 PC-064402 from the U.S. National Cancer Institute and Food and Drug Administration Center for Tobacco Products. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or the Food and Drug Administration. Mass spectrometry was carried out in the Analytical Biochemistry Shared Resource of the Masonic Cancer Center, University of Minnesota, supported in part by Cancer Center Support Grant CA-077598. Publisher Copyright: {\textcopyright} 2020 Elsevier B.V.",

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AU - Reisinger, Sarah A.

AU - Shields, Peter G.

AU - Hatsukami, Dorothy K.

AU - Balbo, Silvia

AU - Hecht, Stephen S.

N1 - Funding Information: This study was supported by grants CA-138338 from the U.S. National Cancer Institute and CA-203851 and N01 PC-064402 from the U.S. National Cancer Institute and Food and Drug Administration Center for Tobacco Products. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or the Food and Drug Administration. Mass spectrometry was carried out in the Analytical Biochemistry Shared Resource of the Masonic Cancer Center, University of Minnesota , supported in part by Cancer Center Support Grant CA-077598 . Funding Information: This study was supported by grants CA-138338 from the U.S. National Cancer Institute and CA-203851 and N01 PC-064402 from the U.S. National Cancer Institute and Food and Drug Administration Center for Tobacco Products. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or the Food and Drug Administration. Mass spectrometry was carried out in the Analytical Biochemistry Shared Resource of the Masonic Cancer Center, University of Minnesota, supported in part by Cancer Center Support Grant CA-077598. Publisher Copyright: © 2020 Elsevier B.V.

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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.

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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

Abstract

Bibliographical note

Keywords

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