Stable Isotope-Assisted Metabolomics for Deciphering Xenobiotic Metabolism in Mammalian Cell Culture. 2020

Mira Flasch, and Christoph Bueschl, and Lydia Woelflingseder, and Heidi E Schwartz-Zimmermann, and Gerhard Adam, and Rainer Schuhmacher, and Doris Marko, and Benedikt Warth
Department of Food Chemistry and Toxicology, Faculty of Chemistry, University of Vienna, Währinger Straße 38, 1090 Vienna, Austria.

Xenobiotics are ubiquitous in the environment and modified in the human body by phase I and II metabolism. Liquid chromatography coupled to high resolution mass spectrometry is a powerful tool to investigate these biotransformation products. We present a workflow based on stable isotope-assisted metabolomics and the bioinformatics tool MetExtract II for deciphering xenobiotic metabolites produced by human cells. Its potential was demonstrated by the investigation of the metabolism of deoxynivalenol (DON), an abundant food contaminant, in a liver carcinoma cell line (HepG2) and a model for colon carcinoma (HT29). Detected known metabolites included DON-3-sulfate, DON-10-sulfonate 2, and DON-10-glutathione as well as DON-cysteine. Conjugation with amino acids and an antibiotic was confirmed for the first time. The approach allows the untargeted elucidation of human xenobiotic products in tissue culture. It may be applied to other fields of research including drug metabolism, personalized medicine, exposome research, and systems biology to better understand the relevance of in vitro experiments.

UI MeSH Term Description Entries
D007553 Isotope Labeling Techniques for labeling a substance with a stable or radioactive isotope. It is not used for articles involving labeled substances unless the methods of labeling are substantively discussed. Tracers that may be labeled include chemical substances, cells, or microorganisms. Isotope Labeling, Stable,Isotope-Coded Affinity Tagging,Isotopically-Coded Affinity Tagging,Affinity Tagging, Isotope-Coded,Affinity Tagging, Isotopically-Coded,Isotope Coded Affinity Tagging,Labeling, Isotope,Labeling, Stable Isotope,Stable Isotope Labeling,Tagging, Isotope-Coded Affinity,Tagging, Isotopically-Coded Affinity
D002247 Carbon Isotopes Stable carbon atoms that have the same atomic number as the element carbon but differ in atomic weight. C-13 is a stable carbon isotope. Carbon Isotope,Isotope, Carbon,Isotopes, Carbon
D002853 Chromatography, Liquid Chromatographic techniques in which the mobile phase is a liquid. Liquid Chromatography
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D014255 Trichothecenes Usually 12,13-epoxytrichothecenes, produced by Fusaria, Stachybotrys, Trichoderma and other fungi, and some higher plants. They may contaminate food or feed grains, induce emesis and hemorrhage in lungs and brain, and damage bone marrow due to protein and DNA synthesis inhibition. Epoxytrichothecenes,Trichothecene Epoxides,Epoxides, Trichothecene
D015262 Xenobiotics Chemical substances that are foreign to the biological system. They include naturally occurring compounds, drugs, environmental agents, carcinogens, insecticides, etc. Xenobiotic
D045744 Cell Line, Tumor A cell line derived from cultured tumor cells. Tumor Cell Line,Cell Lines, Tumor,Line, Tumor Cell,Lines, Tumor Cell,Tumor Cell Lines
D053719 Tandem Mass Spectrometry A mass spectrometry technique using two (MS/MS) or more mass analyzers. With two in tandem, the precursor ions are mass-selected by a first mass analyzer, and focused into a collision region where they are then fragmented into product ions which are then characterized by a second mass analyzer. A variety of techniques are used to separate the compounds, ionize them, and introduce them to the first mass analyzer. For example, for in GC-MS/MS, GAS CHROMATOGRAPHY-MASS SPECTROMETRY is involved in separating relatively small compounds by GAS CHROMATOGRAPHY prior to injecting them into an ionization chamber for the mass selection. Mass Spectrometry-Mass Spectrometry,Mass Spectrometry Mass Spectrometry,Mass Spectrometry, Tandem
D055432 Metabolomics The systematic identification and quantitation of all the metabolic products of a cell, tissue, organ, or organism under varying conditions. The METABOLOME of a cell or organism is a dynamic collection of metabolites which represent its net response to current conditions. Metabonomics,Metabolomic,Metabonomic
D055442 Metabolome The dynamic collection of metabolites which represent a cell's or organism's net metabolic response to current conditions. Metabolic Profile,Metabolic Profiles,Metabolomes,Profile, Metabolic,Profiles, Metabolic

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