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Development of a targeted adductomic method for the determination of polycyclic aromatic hydrocarbon DNA adducts using online column-switching liquid chromatography/tandem mass spectrometry

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journal contribution
posted on 23.07.2010, 09:19 by Rajinder Singh, Friederike Teichert, Albrecht Seidel, Jonathan Roach, Rebecca Cordell, Mai-Kim Cheng, Heinrich Frank, William P. Steward, Margaret M. Manson, Peter B. Farmer
Human exposure to polycyclic aromatic hydrocarbons (PAHs) from sources such as industrial or urban air pollution, tobacco smoke and cooked food is not confined to a single compound, but instead to mixtures of different PAHs. The interaction of different PAHs may lead to additive, synergistic or antagonistic effects in terms of DNA adduct formation and carcinogenic activity resulting from changes in metabolic activation to reactive intermediates and DNA repair. The development of a targeted DNA adductomic approach using liquid chromatography/tandem mass spectrometry (LC/MS/MS) incorporating software-based peak picking and integration for the assessment of exposure to mixtures of PAHs is described. For method development PAH-modified DNA samples were obtained by reaction of the anti-dihydrodiol epoxide metabolites of benzo[a]pyrene, benzo[b]fluoranthene, dibenzo[a,l]pyrene (DB[a,l]P) and dibenz[a,h]anthracene with calf thymus DNA in vitro and enzymatically hydrolysed to 2 -deoxynucleosides. Positive LC/electrospray ionisation (ESI)-MS/MS collision-induced dissociation product ion spectra data showed that the majority of adducts displayed a common fragmentation for the neutral loss of 116 u (2 -deoxyribose) resulting in a major product ion derived from the adducted base. The exception was the DB[a,l]P dihydrodiol epoxide adduct of 2 -deoxyadenosine which resulted in major product ions derived from the PAH moiety being detected. Specific detection of mixtures of PAH-adducted 2 -deoxynucleosides was achieved using online column-switching LC/MS/MS in conjunction with selected reaction monitoring (SRM) of the [M+H]+ to [M+H-116]+ transition plus product ions derived from the PAH moiety for improved sensitivity of detection and a comparison was made to detection by constant neutral loss scanning. In conclusion, different PAH DNA adducts were detected by employing SRM [M+H-116]+ transitions or constant neutral loss scanning. However, for improved sensitivity of detection optimised SRM transitions relating to the PAH moiety product ions are required for certain PAH DNA adducts for the development of targeted DNA adductomic methods.

History

Citation

Rapid Communications in Mass Spectrometry, 2010, 24 (16), pp. 2329-2340

Published in

Rapid Communications in Mass Spectrometry

Publisher

Wiley-Blackwell

issn

0951-4198

Available date

23/07/2010

Publisher version

http://onlinelibrary.wiley.com/doi/10.1002/rcm.4645/abstract

Notes

This is the pre-peer reviewed version of the following article: Rapid Communications in Mass Spectrometry, 2010, 24 (16), pp. 2329-2340, which has been published in final form at www3.interscience.wiley.com, Doi: 10.1002/rcm.4645

Language

en