A novel malic acid-enhanced method for the analysis of 5-methyl-2′-deoxycytidine, 5-hydroxymethyl-2′-deoxycytidine, 5-methylcytidine and 5-hydroxymethylcytidine in human urine using hydrophilic interaction liquid chromatography-tandem mass spectrometry

Guo, Cheng; Xie, Cong; Chen, Qin; Cao, Xiaoji; Guo, Mengzhe; Zheng, Shu; Wang, Yinsheng

doi:10.1016/j.aca.2018.06.081

Cited by 42 publications

(31 citation statements)

References 47 publications

(54 reference statements)

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“…The methylation product of cytidine, 5-methylcytidine (5-MeCyt), has also been quantified as an epigenetic marker of RNA, and reduced levels of this modified nucleoside have been found to be associated with various tumors [11]. This oxidation process can also involve lipids and proteins: For proteins, it implies the introduction of functional groups that could alter their functionality and metabolism.…”

Section: Introductionmentioning

confidence: 99%

Urinary Oxidative Stress Biomarkers in Workers of a Titanium Dioxide Based Pigment Production Plant

Buonaurio

Astolfi

Canepari

et al. 2020

IJERPH

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Titanium dioxide is produced or imported into the EU for over one million tons/year. The International Agency for Research on Cancer (IARC) classification is 2B, a possible inhalation carcinogen for humans. This study evaluates urinary biomarkers of oxidative stress in workers of a plant producing TiO2 pigment powder, having 0.25 µm average particle size and an ultrafine fraction, compared to unexposed subjects. Urine samples were collected from forty workers before and after the shift, from six employees of the same company and eighteen volunteers from the same geographical area. Titanium and other metals concentrations were measured by ICP-MS, while DNA, RNA, and protein oxidation products by HPLC/MS-MS. A statistically significant increase was found for the urinary concentration of Al, Cd, Cr, Cu, Fe, Mn, Pb, Ti, and Zr, and for all biomarkers of oxidative stress in post-shift workers’ urine samples. Urinary concentrations after the working shift were higher than for employees and volunteers pooled together for Cd, Mn, and Zr, and for the oxidative stress biomarkers 8-oxoGuo, 8-oxodGuo, and 3NO2Tyr. Biomonitoring studies on dose and effect biomarkers for TiO2 occupational exposure provide information useful for protecting workers’ health even in conditions that comply with health and safety standards, highlighting reversible effects of chronic exposure at very low doses.

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Section: Introductionmentioning

confidence: 99%

Urinary Oxidative Stress Biomarkers in Workers of a Titanium Dioxide Based Pigment Production Plant

Buonaurio

Astolfi

Canepari

et al. 2020

IJERPH

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“…In this respect, methods including 32 P-postlabeling assay, excision assay, and immunoblot analysis have been used for measuring the levels and assessing the repair of targeted DNA lesions in vitro and in vivo. 31,32 Due to its high sensitivity and its capacity in providing structural information, 18,[33][34][35][36][37][38][39][40][41] mass spectrometry has become a tool of choice in DNA adduct analysis. In this vein, solid-phase extraction followed by LC-MS/MS analysis was previously used for quantifying several pyridyloxobutyl and pyridylhydroxybutyl DNA lesions.…”

Section: Introductionmentioning

confidence: 99%

Quantification of DNA Lesions Induced by 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol in Mammalian Cells

Guo

Leng

Tan

et al. 2019

Chem. Res. Toxicol.

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Quantitative measurement of DNA adducts in carcinogen-exposed cells provides the information about the frequency of formation and the rate of removal of DNA lesions in vivo, which yields insights into the initial events of mutagenesis. Metabolic activation of tobacco-specific nitrosamines, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and its reduction product 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), leads to pyridyloxobutylation and pyridylhydroxybutylation of DNA. In this study, we employed a highly robust nanoflow liquid chromatography-nanoelectrospray ionization-tandem mass spectrometry (nLC-nESI-MS/MS) coupled with the isotope-dilution method for simultaneous quantification of O 6-[4-(3-pyridyl)-4hydroxylbut-1-yl]-2′-deoxyguanosine (O 6-PHBdG) and O 2-and O 4-[4-(3-pyridyl)-4hydroxylbut-1-yl]-thymidine (O 2-PHBdT and O 4-PHBdT). Cultured mammalian cells were exposed to a model pyridylhydroxybutylating agent, 4-(acetoxymethylnitrosamino)-1-(3pyridyl)-1-butanol (NNALOAc), followed by DNA extraction, enzymatic digestion, and sample enrichment prior to nLC-nESI-MS/MS quantification. Our results demonstrate, for the first time, that O 4-PHBdT is quantifiable in cellular DNA and naked DNA upon NNALOAc exposure. We also show that nucleotide excision repair (NER) machinery may counteract the formation of O 2-PHBdT and O 4-PHBdT, and O 6-alkylguanine DNA alkyltransferase (AGT) may be responsible for the repair of O 6-PHBdG and O 4-PHBdT in mammalian cells. Together, our study provides new knowledge about the occurrence and repair of NNAL-induced DNA lesions in mammalian cells.

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“…Although other analytical methods, e.g., enzyme-linked immunosorbent assay (ELISA), were utilized to analyze 8-OHdG and 8-OHG (Kobayashi et al, 2015 ; Sliwinska et al, 2016 ), the limited specificity which often leads to the overestimation of the concentrations is a major problem. As a powerful analytical tool, the stable isotope dilution LC-MS/MS technique can achieve high accuracy because the analyte loss during the pretreatment procedure and the ionization efficiency of analytes in mass spectrometer are compensated (Guo et al, 2018a ). In order to improve the separation efficiency and make the analysis time shorter, substitution of conventional high-performance liquid chromatography (HPLC) by ultra-performance liquid chromatography (UPLC) is a commonly used strategy.…”

Section: Introdutionmentioning

confidence: 99%

Elevated Levels of Oxidative Nucleic Acid Modification Markers in Urine From Gastric Cancer Patients: Quantitative Analysis by Ultra Performance Liquid Chromatography-Tandem Mass Spectrometry

Chen

Fang

et al. 2020

Front. Chem.

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Oxidative nucleic acid modifications have attracted increasing attention in recent years since they have been found to be related to a number of diseases including cancer. 8-Hydroxy-2′-deoxyguanosine (8-OHdG) and 8-hydroxyguanosine (8-OHG) are the typical markers of oxidative modification of DNA and RNA, respectively, and they are emerging biomarkers for the early detection of diseases. Urine is a favored biofluid for biomarker discovery due to its noninvasiveness to patients. Accurate quantification of these oxidative nucleic acid modifications still has challenges because their amounts in urine are very low and the interferences in urine samples are complicated. Herein, we developed and validated an accurate and robust solid-phase extraction (SPE) coupled with ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the simultaneous quantification of these oxidative nucleic acid modifications in human urine. Stable isotope dilution strategy was utilized and the method shows good precision on intraday and interday measurements. Meanwhile, recovery was satisfactory by utilizing the Oasis hydrophilic–lipophilic balance (HLB) cartridge for sample pretreatment at three spiked levels. We successfully quantified urinary 8-OHdG and 8-OHG from 60 gastric cancer patients and 70 healthy controls by using this method. The measured contents of 8-OHdG and 8-OHG in urine from gastric cancer patients are both increased, compared with those in urine from healthy controls, indicating these oxidative nucleic acid modifications could act as potential non-invasive markers for early diagnosis of gastric cancer. Moreover, the present study will stimulate investigations of the effects of oxidative stress and nucleic acid modifications on the initiation and progression of gastric cancer.

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A novel malic acid-enhanced method for the analysis of 5-methyl-2′-deoxycytidine, 5-hydroxymethyl-2′-deoxycytidine, 5-methylcytidine and 5-hydroxymethylcytidine in human urine using hydrophilic interaction liquid chromatography-tandem mass spectrometry

Cited by 42 publications

References 47 publications

Urinary Oxidative Stress Biomarkers in Workers of a Titanium Dioxide Based Pigment Production Plant

Urinary Oxidative Stress Biomarkers in Workers of a Titanium Dioxide Based Pigment Production Plant

Quantification of DNA Lesions Induced by 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol in Mammalian Cells

Elevated Levels of Oxidative Nucleic Acid Modification Markers in Urine From Gastric Cancer Patients: Quantitative Analysis by Ultra Performance Liquid Chromatography-Tandem Mass Spectrometry

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