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Mass Spectrometric DNA Adduct Quantification by Multiple Reaction Monitoring and Its Future Use for the Molecular Epidemiology of Cancer

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Advancements of Mass Spectrometry in Biomedical Research

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 806))

Abstract

The formation of DNA adducts is considered essential for tumor initiation. Quantification of DNA adducts may be achieved by various techniques of which LC-MS/MS-based multiple reaction monitoring has become the most prominent in the past decade. Adducts of single nucleosides are analyzed following enzymatic break-down of a DNA sample following adduct enrichment usually by solid-phase extraction. LC-MS/MS quantification is carried out using stable isotope-labeled internal reference substances. An upcoming challenge is the use of DNA adducts as biomarkers either for internal exposure to electrophilic genotoxins or for the approximation of cancer risk. Here we review recent studies in which DNA adducts were quantified by LC-MS/MS in DNA samples from human matrices. We outline a possible way for future research to aim at the development of an “adductome” approach for the characterization of DNA adduct spectra in human tissues. The DNA adduct spectrum reflects the inner exposure of an individual’s tissue to electrophilic metabolites and, therefore, should replace the conventional and inaccurate external exposure in epidemiological studies in the future.

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Abbreviations

2-AAF:

2-Acetylaminofluorene

4-ABP:

4-Aminobiphenyl

BaP:

Benzo[a]pyrene

CYP:

Cytochrome P450 monooxygenase

dA:

2′-Deoxyadenosine

dC:

2′-Deoxycytidine

dG:

2′-Deoxyguanosine

HAA:

Heterocyclic aromatic amine

LC-MS/MS:

Liquid chromatography—tandem mass spectrometry

MP:

1-Methylpyrene

MRM:

Multiple reaction monitoring

PAH:

Polycyclic aromatic hydrocarbon

PhIP:

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine

TLC:

Thin-layer chromatography

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Acknowledgments

The author gratefully acknowledges financial support from the German Research Foundation (MO 2520/1-1) and the German Institute of Human Nutrition (DIfE).

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Authors and Affiliations

  1. Lead, Genotoxic Food Contaminants Research Group, German Institute of Human Nutrition (DIfE) Potsdam-Rehbrücke, Arthur-Scheunert-Allee 114-116, 14558, Nuthetal, Germany

    Bernhard H. Monien

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  1. Bernhard H. Monien
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Correspondence to Bernhard H. Monien .

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Editors and Affiliations

  1. Chemistry and Biomolecular Science Biochemistry and Proteomics Group, Clarkson University, Potsdam, New York, USA

    Alisa G. Woods

  2. Chemistry and Biomolecular Science Biochemistry and Proteomics Group, Clarkson University, Potsdam, New York, USA

    Costel C. Darie

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Monien, B.H. (2014). Mass Spectrometric DNA Adduct Quantification by Multiple Reaction Monitoring and Its Future Use for the Molecular Epidemiology of Cancer. In: Woods, A., Darie, C. (eds) Advancements of Mass Spectrometry in Biomedical Research. Advances in Experimental Medicine and Biology, vol 806. Springer, Cham. https://doi.org/10.1007/978-3-319-06068-2_18

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