Stable Isotope-Assisted Metabolomics for Deciphering Xenobiotic Metabolism in Mammalian Cell Culture
| Autor: | Gerhard Adam, H.E. Schwartz-Zimmermann, Lydia Woelflingseder, Christoph Bueschl, Rainer Schuhmacher, Mira Flasch, Benedikt Warth, Doris Marko |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Exposome Systems biology 01 natural sciences Biochemistry Xenobiotics 03 medical and health sciences chemistry.chemical_compound Tissue culture Metabolomics Biotransformation Tandem Mass Spectrometry Cell Line Tumor Humans Carbon Isotopes 010405 organic chemistry Computational Biology General Medicine Articles 0104 chemical sciences 030104 developmental biology chemistry Cell culture Isotope Labeling Metabolome Molecular Medicine Xenobiotic Trichothecenes Drug metabolism Chromatography Liquid |
| Zdroj: | ACS Chemical Biology |
| ISSN: | 1554-8937 1554-8929 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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