Screening DNA Adducts by LC–ESI–MS–MS: Application to Screening New Adducts Formed from Acrylamide

Inagaki, Shinsuke; Hirashima, Haruo; Esaka, Yukihiro; Higashi, Tatsuya; Min, Jun Zhe; Toyo’oka, Toshimasa

doi:10.1365/s10337-010-1783-7

Cited by 18 publications

(28 citation statements)

References 20 publications

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“…Inagaki et al 143 employed an adductomics approach to discover novel DNA adducts of acrylamide (AM). Calf thymus DNA was treated with the ultimate reactive metabolite of AM, glycidamide, and the alkylated DNA was acid hydrolyzed with HCl to release purine bases.…”

Section: New Analytical Approaches For Dna Adduct Analysismentioning

confidence: 99%

“…These analyses have detected known adducts, N1-(2-carboxy-2- hydroxyethyl)-N7-(2-carbamoyl-2-hydroxyethyl)-guanine (Chart 7), as well as several previously unknown AM-DNA lesions. 143 Spillberg et al employed a similar tandem mass spectrometry-based approach to identify 90 damaged nucleosides derived from dietary DNA. 144 …”

Section: New Analytical Approaches For Dna Adduct Analysismentioning

confidence: 99%

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Quantitation of DNA Adducts by Stable Isotope Dilution Mass Spectrometry

Tretyakova

Goggin

Sangaraju

et al. 2012

Chem. Res. Toxicol.

107

125

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Exposure to endogenous and exogenous chemicals can lead to the formation of structurally modified DNA bases (DNA adducts). If not repaired, these nucleobase lesions can cause polymerase errors during DNA replication, leading to heritable mutations and potentially contributing to the development of cancer. Because of their critical role in cancer initiation, DNA adducts represent mechanism-based biomarkers of carcinogen exposure, and their quantitation is particularly useful for cancer risk assessment. DNA adducts are also valuable in mechanistic studies linking tumorigenic effects of environmental and industrial carcinogens to specific electrophilic species generated from their metabolism. While multiple experimental methodologies have been developed for DNA adduct analysis in biological samples, including immunoassay, HPLC, and 32P-postlabeling, isotope dilution high performance liquid chromatography–electrospray ionization–tandem mass spectrometry (HPLC-ESI-MS/MS) generally has superior selectivity, sensitivity, accuracy, and reproducibility. As typical DNA adduct concentrations in biological samples are between 0.01–10 adducts per 108 normal nucleotides, ultrasensitive HPLC-ESI-MS/MS methodologies are required for their analysis. Recent developments in analytical separations and biological mass spectrometry, especially nanoflow HPLC, nanospray ionization MS, chip-MS, and high resolution MS, have pushed the limits of analytical HPLC-ESI-MS/MS methodologies for DNA adducts, allowing researchers to accurately measure their concentrations in biological samples from patients treated with DNA alkylating drugs and in populations exposed to carcinogens from urban air, drinking water, cooked food, alcohol, and cigarette smoke.

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Section: New Analytical Approaches For Dna Adduct Analysismentioning

confidence: 99%

Section: New Analytical Approaches For Dna Adduct Analysismentioning

confidence: 99%

Quantitation of DNA Adducts by Stable Isotope Dilution Mass Spectrometry

Tretyakova

Goggin

Sangaraju

et al. 2012

Chem. Res. Toxicol.

107

125

View full text Add to dashboard Cite

show abstract

“…[12][13][14] More than a decade ago Koc et al stated that the only disadvantage of MS in the field of DNA adduct analysis, was its sensitivity. 28 Over the years, sensitivity has continued to improve 6,14 as different research groups have focused on optimization of DNA adduct detection methods with MS [30][31][32][33][34][35][36][37] , including research into non-manual data mining and sequencing to locate DNA adduction sites. 38,39 Due to ongoing technical advancements and the use of stable isotope labeled internal standards, MS currently offers a reliable tool to measure low DNA adduct levels with the highest specificity.…”

Section: Mass Spectrometry As the Methods Of Choice For Dna Adductomicsmentioning

confidence: 99%

Mass Spectrometric Mapping of the DNA Adductome as a Means to Study Genotoxin Exposure, Metabolism, and Effect

2016

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Covalent binding of endo-or exogenous chemicals to DNA results in the formation of DNA adducts which are reflective of exposure of the human body to DNA-damaging molecules and their metabolic pathways. The study of DNA adduct types and levels in human tissue therefore offers an interesting tool in several fields of research, including toxicology and cancer epidemiology. Over the years, a range of techniques and methods have been developed to study the formation of endo-and exogenous DNA adducts. However, for the simultaneous detection, identification and quantification of both known and unknown DNA adducts, mass spectrometry (MS) is deemed to be the most promising technique. In this perspective, we focus on the analysis of multiple DNA adducts within a sample with the emphasis on untargeted analysis. The advantageous use of MS methodologies for DNA adductome mapping is discussed comprehensively with relevant field examples. In addition, several aspects of study design, sample pretreatment and analysis are addressed as these factors significantly affect the reliability of DNA adductomics studies.

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“…[34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51] However, the sensitive determination of negatively charged molecules, such as carboxylic acids, is not always promising in spite of the highly sensitive MS detection. 52,53 In such a case, the derivatization technique, which generally uses a basic reagent possessing amine(s), is effective for increasing the detection sensitivity and separation efficiency of reversed-phase chromatography, 54 because the resulting derivatives are easily charged as a cation by acidic mobile-phase containing formic and acetic acids.…”

Section: Reagents For Amines and Carboxylic Acidsmentioning

confidence: 99%

Derivatization-based High-throughput Bioanalysis by LC-MS

Toyo’oka

2017

ANAL. SCI.

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Liquid chromatography coupled with mass spectrometry (LC-MS) is one of the most prominent analytical techniques due to its inherent selectivity and sensitivity. LC-MS is currently the first choice for high-throughput bioanalysis due to the advancements in MS instruments and the analytical software. Based on this situation, we are developing various types of derivatization reagents, including chiral reagents for MS and/or MS/MS detection. These developed reagents are adopted for the detection of biomarker candidates related to diseases. The biomarker candidates include not only achiral molecules, but also chiral ones. Although determining the already-identified chiral molecules is relative easy, it is very difficult to identify and/or determine unknown enantiomer(s) in real samples. To solve this difficulty, we proposed a new strategy to identify unknown enantiomeric biomarkers related to diseases. This review paper deals with the development of derivatization reagents for amines and carboxylic acids in LC-MS analysis and their application to bioanalysis.

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Screening DNA Adducts by LC–ESI–MS–MS: Application to Screening New Adducts Formed from Acrylamide

Cited by 18 publications

References 20 publications

Quantitation of DNA Adducts by Stable Isotope Dilution Mass Spectrometry

Quantitation of DNA Adducts by Stable Isotope Dilution Mass Spectrometry

Mass Spectrometric Mapping of the DNA Adductome as a Means to Study Genotoxin Exposure, Metabolism, and Effect

Derivatization-based High-throughput Bioanalysis by LC-MS

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