Journal Article

Liquid chromatography-electrospray ionization-mass spectrometry: the future of DNA adduct detection

Rajinder Singh and Peter B. Farmer

in Carcinogenesis

Volume 27, issue 2, pages 178-196
Published in print February 2006 | ISSN: 0143-3334
Published online November 2005 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgi260
Liquid chromatography-electrospray ionization-mass spectrometry: the future of DNA adduct detection

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Over the past 40 years considerable emphasis has been placed on the development of accurate and sensitive methods for the detection and quantitation of DNA adducts. The formation of DNA adducts resulting from the covalent interaction of genotoxic carcinogens with DNA, derived from exogenous and endogenous sources, either directly or following metabolic activation, can if not repaired lead to mutations in critical genes such as those involved in the regulation of cellular growth and subsequent development of cancer. The major analytical challenge has been to detect levels of DNA adducts at the level of 0.1–1 adducts per 108 unmodified DNA bases using only low microgram amounts of DNA, and with high specificity and accuracy, in humans exposed to genotoxic carcinogens derived from occupational, environmental, dietary and life-style sources. In this review we will highlight the merits as well as discuss the progress made by liquid chromatography coupled to electrospray ionization mass spectrometry as a method for DNA adduct detection.

Keywords: APCI, atmospheric pressure chemical ionization; CE, capillary electrophoresis; CID, collision induced dissociation; CNL, constant neutral loss; ESI, electrospray ionization; GC-MS, gas chromatography-mass spectrometry; HPLC, high performance liquid chromatography; LC, liquid chromatography; MS, mass spectrometry; MS/MS, tandem mass spectrometry; N-7(2-OHEt)G, N-7 (2-hydroxyethyl)guanine; PAHs, polycyclic aromatic hydrocarbons; PhIP, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine; SIM, single ion monitoring; SRM, selected reaction monitoring; TOF, time-of-flight

Journal Article.  17036 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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