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.

中文翻译：

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稳定的同位素辅助代谢组学，用于解释哺乳动物细胞培养物中的异种生物代谢。

异生物素在环境中无处不在，并且在人体中通过I和II期代谢而被修饰。液相色谱与高分辨率质谱联用是研究这些生物转化产物的有力工具。我们提出了一种基于稳定同位素辅助代谢组学和生物信息学工具MetExtract II的工作流程，用于破译人类细胞产生的异源代谢物。通过对肝癌细胞系（HepG2）和结肠癌模型（HT29）中丰富的食物污染物脱氧雪腐烯醇（DON）的代谢研究，证明了其潜力。检测到的已知代谢物包括DON-3-硫酸盐，DON-10-磺酸盐2和DON-10-谷胱甘肽以及DON-半胱氨酸。首次确认了与氨基酸和抗生素的结合。该方法允许在组织培养中无目标地阐明人类异种产品。它可以应用于其他研究领域，包括药物代谢，个性化医学，暴露研究和系统生物学，以更好地了解体外实验的相关性。