Quantitation of Lipid Peroxidation Product DNA Adducts in Human Prostate by Tandem Mass Spectrometry: A Method That Mitigates Artifacts

Haoqing Chen, Sesha Krishnamachari, Jingshu Guo, Lihua Yao, Paari Murugan, Christopher J. Weight, Robert J. Turesky

Research output: Contribution to journalArticle

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Abstract

Reactive oxygen species (ROS) and chronic inflammation contribute to DNA damage of many organs, including the prostate. ROS cause oxidative damage to biomolecules, such as lipids, proteins, and nucleic acids, resulting in the formation of toxic and mutagenic intermediates. Lipid peroxidation (LPO) products covalently adduct to DNA and can lead to mutations. The levels of LPO DNA adducts reported in humans range widely. However, a large proportion of the DNA adducts may be attributed to artifact formation during the steps of isolation and nuclease digestion of DNA. We established a method that mitigates artifacts for most LPO adducts during the processing of DNA. We have applied this methodology to measure LPO DNA adducts in the genome of prostate cancer patients, employing ultrahigh-performance liquid chromatography electrospray ionization ion trap multistage mass spectrometry. Our preliminary data show that DNA adducts of acrolein, 6-hydroxy-1,N2-propano-2′-deoxyguanosine (6-OH-PdG) and 8-hydroxy-1,N2-propano-2′-deoxyguanosine (8-OH-PdG) (4-20 adducts per 107 nucleotides) are more prominent than etheno (ϵ) adducts (<0.5 adducts per 108 nucleotides). This analytical methodology will be used to examine the correlation between oxidative stress, inflammation, and LPO adduct levels in patients with benign prostatic hyperplasia and prostate cancer.

Original languageEnglish (US)
Pages (from-to)1850-1862
Number of pages13
JournalChemical research in toxicology
Volume32
Issue number9
DOIs
StatePublished - Sep 16 2019

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DNA Adducts
Tandem Mass Spectrometry
Artifacts
Lipid Peroxidation
Mass spectrometry
Prostate
Lipids
Prostatic Neoplasms
Reactive Oxygen Species
Nucleotides
DNA
Inflammation
Acrolein
Deoxyribonucleases
Poisons
Prostatic Hyperplasia
Electrospray ionization
Oxidative stress
Liquid Chromatography
Nucleic Acids

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Quantitation of Lipid Peroxidation Product DNA Adducts in Human Prostate by Tandem Mass Spectrometry : A Method That Mitigates Artifacts. / Chen, Haoqing; Krishnamachari, Sesha; Guo, Jingshu; Yao, Lihua; Murugan, Paari; Weight, Christopher J.; Turesky, Robert J.

In: Chemical research in toxicology, Vol. 32, No. 9, 16.09.2019, p. 1850-1862.

Research output: Contribution to journalArticle

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