The application of mass spectrometry in molecular dosimetry: Ethylene oxide as an example

Wu, Kuen-Yuh; Chiang, Su‐Yin; Shih, Wen‐Pin; Huang, Chih Chun Jean; Chen, Ming Feng; Swenberg, James A.

doi:10.1002/mas.20299

Cited by 18 publications

(19 citation statements)

References 154 publications

(213 reference statements)

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“…12,14,27,28 Coupling of MS with LC by means of the electrospray interface (ESI) has enabled analysis of DNA adducts in very complex biological matrices 40 , whilst avoiding complex and labour-intensive sample preparation with derivatization for the initially envisioned use of GCcouplings. 41 An important advantage of MS, in contrast to all other previously mentioned DNA adduct detection methods (besides NMR), is the possibility to detect both 'targeted' and 'untargeted' DNA adducts by means of full scan MS. Targeted DNA adduct detection (also known as 'profiling') refers to the detection of known types of DNA adducts, which implies that the MS system specifically scans for the presence of certain compounds of interest to assess their presence and abundance, whilst all other molecules in the sample are disregarded completely.…”

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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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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“…Alternative less common radiation sterilization methods such as UV light are also detrimental for peptides [151]. Due to high reactivity of ethylene oxide, it easily forms hydroxyethylated adducts with many amino acids, in particular such adducts were identified with cysteine, methionine, histidine and N-terminal valine [152, 153]. …”

Section: Antimicrobial Peptides (Amps) – Promising Therapeutics Fomentioning

confidence: 99%

Beyond conventional antibiotics — New directions for combination products to combat biofilm

Bayramov

Neff

2017

Advanced Drug Delivery Reviews

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Medical device related infections are a significant and growing source of morbidity and mortality. Biofilm formation is a common feature of medical device infections that is not effectively prevented or treated by systemic antibiotics. Antimicrobial medical device combination products provide a pathway for local delivery of antimicrobial therapeutics with the ability to achieve high local concentrations while minimizing systemic side effects. In this review, we present considerations for the design of local antimicrobial delivery systems, which can be facilitated by modeling local pharmacokinetics in the context of the target device application. In addition to the need for local delivery, a critical barrier to progress in the field is the need to incorporate agents effective against biofilm. This article aims to review key properties of antimicrobial peptides that make them well suited to meet the demands of the next generation of antimicrobial medical devices, including broad spectrum activity, rapid and biocidal mechanisms of action, and efficacy against biofilm.

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“…The endogenous production of ethylene results from oxidative stress [64] and from gut microflora [65]. Endogenous ethylene circulates in the blood and is metabolized to EO in the liver [66], which also circulates in the body. Endogenous EO forms N7-(2-hydroxyethyl)guanine adducts as shown in Table 1.…”

Section: Ethylene/ethylene Oxidementioning

confidence: 99%

The endogenous exposome

et al. 2014

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The concept of the Exposome, is a compilation of diseases and one’s lifetime exposure to chemicals, whether the exposure comes from environmental, dietary, or occupational exposures; or endogenous chemicals that are formed from normal metabolism, inflammation, oxidative stress, lipid peroxidation, infections, and other natural metabolic processes such as alteration of the gut microbiome. In this review, we have focused on the Endogenous Exposome, the DNA damage that arises from the production of endogenous electrophilic molecules in our cells. It provides quantitative data on endogenous DNA damage and its relationship to mutagenesis, with emphasis on when exogenous chemical exposures that produce identical DNA adducts to those arising from normal metabolism cause significant increases in total identical DNA adducts. We have utilized stable isotope labeled chemical exposures of animals and cells, so that accurate relationships between endogenous and exogenous exposures can be determined. Advances in mass spectrometry have vastly increased both the sensitivity and accuracy of such studies. Furthermore, we have clear evidence of which sources of exposure drive low dose biology that results in mutations and disease. These data provide much needed information to impact quantitative risk assessments, in the hope of moving towards the use of science, rather than default assumptions.

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The application of mass spectrometry in molecular dosimetry: Ethylene oxide as an example

Cited by 18 publications

References 154 publications

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

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

Beyond conventional antibiotics — New directions for combination products to combat biofilm

The endogenous exposome

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