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Quantitative analysis of malondialdehyde-guanine adducts in genomic DNA samples by liquid chromatography tandem mass spectrometry.

Yates, SA and Dempster, NM and Murphy, MF and Moore, SA (2017) Quantitative analysis of malondialdehyde-guanine adducts in genomic DNA samples by liquid chromatography tandem mass spectrometry. Rapid Communications in Mass Spectrometry. ISSN 0951-4198

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Abstract

RATIONALE: The lipid peroxidation product malondialdehyde forms M1 dG adducts with guanine bases in genomic DNA. The analysis of these adducts is important as a biomarker of lipid peroxidation, oxidative stress and inflammation which may be linked to disease risk or exposure to a range of chemicals. METHODS: Genomic DNA samples were subjected to acid hydrolysis to release the adducts in the base form (M1 G) alongside the other purines. A liquid chromatography-mass spectrometry method was optimised for the quantitation of the M1 G adducts in genomic DNA samples using product ion and multiple reaction mode scans. RESULTS: Product ion scans revealed four product ions from the precursor ion; m/z 188 → 160, 133, 106 and 79. The two smallest ions have not been observed previously and optimisation of the method revealed that these gave better sensitivity (LOQ m/z 79: 162 adducts per 10(7) nucleotides; m/z 106: 147 adducts per 10(7) nucleotides) than the other two ions. An MRM method gave similar sensitivity but the two smallest product ions gave better accuracy (94-95%). Genomic DNA treated with malondialdehyde showed a linear dose-response relationship. CONCLUSION: A fast reliable sample preparation method was used to release adducts in the base form rather than the nucleoside. The methods were optimised to selectively analyse the adducts in the presence of other DNA bases without the need for further sample clean-up. Analysis of genomic DNA gave results consistent with previous work and was applied to new samples. Thus, the method is suitable for the analysis of M1 (d)G adducts in biological samples.

Item Type: Article
Additional Information: This is the peer reviewed version of the following article: Yates, S. A., Dempster, N. M., Murphy, M. F., and Moore, S. A. (2017) Quantitative analysis of malondialdehyde-guanine adducts in genomic DNA samples by liquid chromatography tandem mass spectrometry. Rapid Commun. Mass Spectrom., doi: 10.1002/rcm.7843, which has been published in final form at http://dx.doi.org/10.1002/rcm.7843 This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
Uncontrolled Keywords: 03 Chemical Sciences, 04 Earth Sciences, 06 Biological Sciences
Subjects: Q Science > QD Chemistry
R Medicine > RM Therapeutics. Pharmacology
Divisions: Pharmacy & Biomolecular Sciences
Publisher: Wiley
Related URLs:
Date Deposited: 29 Mar 2017 08:37
Last Modified: 29 Mar 2017 08:37
DOI or Identification number: 10.1002/rcm.7843
URI: http://researchonline.ljmu.ac.uk/id/eprint/6139

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