Analysis of 4-Hydroxy-1-(3-pyridyl)-1-butanone (HPB)-Releasing DNA Adducts in Human Exfoliated Oral Mucosa Cells by Liquid Chromatography–Electrospray Ionization–Tandem Mass Spectrometry

Stepanov, Irina; Muzic, John G.; Le, Chap T.; Sebero, Erin; Villalta, Peter W.; Ma, Bin; Jensen, Joni; Hatsukami, Dorothy K.; Hecht, Stephen S.

doi:10.1021/tx300282k

Cited by 37 publications

(74 citation statements)

References 30 publications

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“…To achieve detection limits in the low fmol to amol range (1 per 10 8 –1 per 10 9 nucleotides) as required for our in vivo studies, we employed nanoLC/ESI + -HRMS 3 methodology on an Orbitrap Velos mass spectrometer. We and others have recently reported the use of high resolution mass spectrometry for DNA adduct analysis in complex samples and have shown that it dramatically reduces the matrix background, leading to greatly improved signal to noise ratios [37, 45, 46]. …”

Section: Resultsmentioning

confidence: 99%

NanoLC/ESI⁺ HRMS³ Quantitation of DNA Adducts Induced by 1,3-Butadiene

Sangaraju

Villalta

Wickramaratne

et al. 2014

J. Am. Soc. Mass Spectrom.

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Human exposure to 1,3-butadiene (BD) present in automobile exhaust, cigarette smoke, and forest fires is of great concern because of its potent carcinogenicity. The adverse health effects of BD are mediated by its epoxide metabolites such as 3,4-epoxy-1-butene (EB), which covalently modify genomic DNA to form promutagenic nucleobase adducts. Because of their direct role in cancer, BD-DNA adducts can be used as mechanism-based biomarkers of BD exposure. In the present work, a mass spectrometry-based methodology was developed for accurate, sensitive, and precise quantification of EB-induced N-7-(1-hydroxy-3-buten-2-yl) guanine (EB-GII) DNA adducts in vivo. In our approach, EB-GII adducts are selectively released from DNA backbone by neutral thermal hydrolysis, followed by ultrafiltration, offline HPLC purification, and isotope dilution nanoLC/ESI+-HRMS3 analysis on an Orbitrap Velos mass spectrometer. Following method validation, EB-GII lesions were quantified in human fibrosarcoma (HT1080) cells treated with micromolar concentrations of EB and in liver tissues of rats exposed to sub ppm concentrations of BD (0.5–1.5 ppm). EB-GII concentrations increased linearly from 1.15±0.23 to 10.11±0.45adducts per 108 nucleotides in HT1080 cells treated with 0.5–10 μM DEB. EB-GII concentrations in DNA of laboratory rats exposed to 0.5, 1.0 and 1.5 ppm BD were 0.17±0.05, 0.33±0.08, and 0.50±0.04 adducts per 108 nucleotides, respectively. We also used the new method to determine the in vivo half-life of EB-GII adducts in rat liver DNA (2.20±0.12 days) and to detect EB-GII in human blood DNA. To our knowledge, this is the first application of nanoLC/ESI+-HRMS3 Orbitrap methodology to quantitative analysis of DNA adducts in vivo.

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Section: Resultsmentioning

confidence: 99%

NanoLC/ESI⁺ HRMS³ Quantitation of DNA Adducts Induced by 1,3-Butadiene

Sangaraju

Villalta

Wickramaratne

et al. 2014

J. Am. Soc. Mass Spectrom.

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“…Once activated, NNN leads to formation of pyridyloxobutyl (POB)-DNA adducts [40]. Under strong acid hydrolysis conditions, the majority of POB-DNA adducts decompose to release 4-hydroxy-1-(3-pyridyl)-1-butanone (HPB) [41–43]. In vitro and laboratory animal studies have demonstrated the importance of HPB-releasing adducts in NNK- and NNN-induced carcinogenesis [32,44].…”

Section: Tobacco Carcinogensmentioning

confidence: 99%

Tobacco-related carcinogenesis in head and neck cancer

Jethwa

Khariwala

2017

Cancer Metastasis Rev

225

166

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Head and neck cancer (HNSCC) is a devastating disease. Patients require intensive treatment that is often disfiguring and debilitating. Those who survive are often left with poor speech articulation, difficulties in chewing and swallowing, cosmetic disfigurement, as well as loss of taste. Furthermore, given that HNSCC survivors are frequently disabled and unable to return to work, the economic and societal costs associated with HNSCC are massive. HNSCC is one of many cancers that are strongly associated with tobacco use. The risk for HNSCC in smokers is approximately 10 times higher than that of never-smokers and 70–80% of new HNSCC diagnoses are associated with tobacco and alcohol use. Tobacco products have been used for centuries, however it is just within the last 60–70 years that we have developed an understanding of their damaging effects. This relatively recent understanding has created a pathway towards educational and regulatory efforts aimed at reducing tobacco use. Understanding the carcinogenic components of tobacco products and how they lead to HNSCC is critical to regulatory and harm reduction measures. To date, nitrosamines and other carcinogenic agents present in tobacco products have been associated with cancer development. The disruption of DNA structure through DNA adduct formation is felt to be a common mutagenic pathway of many carcinogens. Intense work pertaining to tobacco product constituents, tobacco use and tobacco regulation has resulted in decreased use in some parts of the world. Still, much work remains as tobacco continues to impart significant harm and contribute to HNSCC development worldwide.

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“…The use of high-resolution MS for the analysis of DNA adducts in complex samples could dramatically reduce the matrix background, leading to greatly improved signal-to-noise (s/n) ratios. 197,216 Likewise, the MS n scan mode also affords better s/n ratio owing to its high specificity, especially when there are co-eluting isobaric interferences. Meanwhile, the method allows for unambiguous identification of analytes of interest as detailed structural information is obtained from additional fragmentation pathways.…”

Section: Quantitative Analysis Of Dna Adductsmentioning

confidence: 99%

“…7 Quantitative analysis of 4-HPB-releasing DNA adducts uncovered these adducts as another robust biomarker to indicate the individual susceptibility to tobacco-induced cancers in humans. 216 …”

Section: Quantitative Analysis Of Dna Adductsmentioning

confidence: 99%

Mass spectrometry for the assessment of the occurrence and biological consequences of DNA adducts

2015

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Exogenous and endogenous sources of chemical species can react, directly or after metabolic activation, with DNA to yield DNA adducts. If not repaired, DNA adducts may compromise cellular functions by blocking DNA replication and/or inducing mutations. Unambiguous identification of the structures and accurate measurements of the levels of DNA adducts in cellular and tissue DNA constitute the first and important step towards understanding the biological consequences of these adducts. The advances in mass spectrometry (MS) instrumentation in the past 2–3 decades have rendered MS an important tool for structure elucidation, quantification, and revelation of the biological consequences of DNA adducts. In this review, we summarized the development of MS techniques on these fronts for DNA adduct analysis. We placed our emphasis of discussion on sample preparation, the combination of MS with gas chromatography-or liquid chromatography (LC)-based separation techniques for the quantitative measurement of DNA adducts, and the use of LC-MS along with molecular biology tools for understanding the human health consequences of DNA adducts. The applications of mass spectrometry-based DNA adduct analysis for predicting the therapeutic outcome of anti-cancer agents, for monitoring the human exposure to endogenous and environmental genotoxic agents, and for DNA repair studies were also discussed.

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Analysis of 4-Hydroxy-1-(3-pyridyl)-1-butanone (HPB)-Releasing DNA Adducts in Human Exfoliated Oral Mucosa Cells by Liquid Chromatography–Electrospray Ionization–Tandem Mass Spectrometry

Cited by 37 publications

References 30 publications

NanoLC/ESI⁺ HRMS³ Quantitation of DNA Adducts Induced by 1,3-Butadiene

NanoLC/ESI⁺ HRMS³ Quantitation of DNA Adducts Induced by 1,3-Butadiene

Tobacco-related carcinogenesis in head and neck cancer

Mass spectrometry for the assessment of the occurrence and biological consequences of DNA adducts

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Analysis of 4-Hydroxy-1-(3-pyridyl)-1-butanone (HPB)-Releasing DNA Adducts in Human Exfoliated Oral Mucosa Cells by Liquid Chromatography–Electrospray Ionization–Tandem Mass Spectrometry

Cited by 37 publications

References 30 publications

NanoLC/ESI+ HRMS3 Quantitation of DNA Adducts Induced by 1,3-Butadiene

NanoLC/ESI+ HRMS3 Quantitation of DNA Adducts Induced by 1,3-Butadiene

Tobacco-related carcinogenesis in head and neck cancer

Mass spectrometry for the assessment of the occurrence and biological consequences of DNA adducts

Contact Info

Product

Resources

About

NanoLC/ESI⁺ HRMS³ Quantitation of DNA Adducts Induced by 1,3-Butadiene

NanoLC/ESI⁺ HRMS³ Quantitation of DNA Adducts Induced by 1,3-Butadiene