title: Multiple biomarkers of the cytotoxicity induced by BDE-47 in human embryonic kidney cells.
abstract: Polybrominated diphenyl ethers (PBDEs) are widely used as brominated flame-retardants in a variety of industrial products. Among these PBDEs, 2,2',4,4'-tetra-bromodiphenyl ether (BDE-47) is one of the most predominant congeners inducing multiple toxicities, including hepatotoxicity, neurotoxicity, cytotoxicity, genotoxicity, carcinogenecity and immunotoxicity in human body. In this study, the cytotoxicity of BDE-47 in human embryonic kidney cells (HEK293) was investigated by a set of bioassays, including cell proliferation, apoptosis, oxidative stress and metabolic responses as well as gene expressions related to apoptosis. Results showed that BDE-47 induced an inverted U-shaped curve of cell proliferation in HEK293 cells from 10(-6) to 10(-4) M. Cell apoptosis and ROS overproduction were detected at 10(-5) M of BDE-47 (p<0.05). In addition, the expressions of Bcl-2 family-encoding genes (Bad, Hrk and Bcl-2) increased significantly in 10(-4)M group (p<0.05). Metabolic responses indicated that BDE-47 mainly caused disturbance in energy metabolism marked by differentially altered ethanol, glutathione, creatine, aspartate, UDP-glucose and NAD(+). The increased lactate/alanine ratios indicated the higher reductive state induced by BDE-47 in all exposures confirmed by the overproduction of ROS.
authors.affiliation: Key Laboratory of Coastal Zone Environmental Processes and Ecological Remediation, Yantai Institute of Coastal Zone Research (YIC), Chinese Academy of Sciences (CAS), Shandong Provincial Key Laboratory of Coastal Zone Environmental Processes, Yantai, Shandong 264003, PR China.
authors.forename: Huifeng
authors.initials: H
authors.lastname: Wu
authors.affiliation: Key Laboratory of Coastal Zone Environmental Processes and Ecological Remediation, Yantai Institute of Coastal Zone Research (YIC), Chinese Academy of Sciences (CAS), Shandong Provincial Key Laboratory of Coastal Zone Environmental Processes, Yantai, Shandong 264003, PR China; University of Chinese Academy of Sciences, Beijing 100049, PR China.
authors.forename: Lulu
authors.initials: L
authors.lastname: Cao
authors.affiliation: Key Laboratory of Coastal Zone Environmental Processes and Ecological Remediation, Yantai Institute of Coastal Zone Research (YIC), Chinese Academy of Sciences (CAS), Shandong Provincial Key Laboratory of Coastal Zone Environmental Processes, Yantai, Shandong 264003, PR China. Electronic address: fli@yic.ac.cn.
authors.forename: Fei
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Center Laboratory, Yantai Yuhuangding Hospital, Yuhuangdingdong Road 20, Yantai 264000, PR China.
authors.forename: Peiwen
authors.initials: P
authors.lastname: Lian
authors.affiliation: Key Laboratory of Coastal Zone Environmental Processes and Ecological Remediation, Yantai Institute of Coastal Zone Research (YIC), Chinese Academy of Sciences (CAS), Shandong Provincial Key Laboratory of Coastal Zone Environmental Processes, Yantai, Shandong 264003, PR China.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Zhao
mesh_terms: D000409:Alanine / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D001224:Aspartic Acid / Q000378:metabolism; D001681:Biological Assay; D015415:Biomarkers / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D003401:Creatine / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects*; D004847:Epithelial Cells / Q000378:metabolism; D000431:Ethanol / Q000378:metabolism; D005411:Flame Retardants / Q000378:metabolism / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D057809:HEK293 Cells; D055768:Halogenated Diphenyl Ethers / Q000378:metabolism / Q000633:toxicity*; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects
chemical_list: D015415:Biomarkers; D005411:Flame Retardants; D055768:Halogenated Diphenyl Ethers; C511295:2,2',4,4'-tetrabromodiphenyl ether; D001224:Aspartic Acid; D019344:Lactic Acid; D000431:Ethanol; D005978:Glutathione; D003401:Creatine; D000409:Alanine
keywords: BDE-47; Cell apoptosis; Cytotoxicity; HEK293 cells; Metabolomics; ROS