Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. (1st November 2017)

• Record Type: Journal Article
• Authors: Liu, Huichang; Cui, Bo; Xu, Yi; Hu, Chaoyang; Liu, Ying; Qu, Guorun; Li, Dawei; Wu, Yongning; Zhang, Dabing; Quan, Sheng; Shi, Jianxin
• Is Part Of: Chemico-biological interactions. Volume 277(2017)
• Page Start: 21
• Page End: 32
• Publication Date: 2017-11-01
• Subjects: Dietary ethyl carbamate -- DNA damage -- Energy depletion -- Membrane integrity -- Oxidative stress; EC ethyl carbamate -- GC-MS gas chromatograph-mass spectrometry -- GO gene ontology -- KEGG Kyoto encyclopedia of genes and genomes -- PPP pentose phosphate pathway -- ROS reactive oxygen species -- CA tricarboxylic acid -- UPLC-MS/MS ultra-performance liquid-chromatography tandem mass spectrometry; Biochemistry -- Periodicals; Toxicological chemistry -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biochimie -- Périodiques; Toxicologie biochimique -- Périodiques; 572
• DOI: 10.1016/j.cbi.2017.08.008
• Languages: English
• ISSNs: 0009-2797

Abstract

Abstract: Ethyl carbamate (EC), a multisite carcinogenic chemical causing tumors in various animal species, is probably carcinogenic to humans. However, information about the possible carcinogenic and toxicological effects of EC in humans is quite limited. Because EC is found in many dietary foods (such as fermented foods) and tobacco and its products, and exposure of humans to EC often occurs inevitably, its toxicological effects in humans need to be studied. This study was conducted to understand the metabolomic and transcriptomic changes in human hepatocellular carcinoma cells (HepG2) exposed to 100 mM EC for short term (4 h) and long term (12 h) period, respectively. The results revealed multiple influences of EC on the metabolome and transcriptome of HepG2 cells, which was exposure time-dependent and well correlated with the kinetic changes of cell viability and mortality. EC treatment affected multiple metabolic pathways, inducing oxidative stress, reducing detoxification capacity, depleting energy, decreasing reducing power, disrupting membrane integrity, and damaging DNA and protein. These metabolomic and transcriptomic biomarkers of EC on human cell metabolism identified in this study would facilitate further studies on the risk assessment and the mitigation of dietary EC. Graphical abstract: Highlights: Ethyl carbamate has profound influences on HepG2 metabolome and transcriptome. Metabolomic and transcriptomic responses of HepG2 are exposure time dependent. Such molecular changes corresponds well with cell's mortality kinetics.