PMID- 29117588 OWN - NLM STAT- MEDLINE DCOM- 20180212 LR - 20181202 IS - 1879-1298 (Electronic) IS - 0045-6535 (Linking) VI - 192 DP - 2018 Feb TI - Metabolic profiling on the effect of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) in MCF-7 cells. PG - 297-304 LID - S0045-6535(17)31756-3 [pii] LID - 10.1016/j.chemosphere.2017.10.170 [doi] AB - Polybrominated diphenyl ethers (PBDEs) are commonly used to prevent the development of fire in various factory products. Due to the adverse effects on human health and the bio-accumulation capacity, PBDEs are considered as one kind of persistent organic pollutants (POPs). BDE-47 is one of the most frequently detected PBDEs congeners in human samples. Although numerous studies have shown the close connection between BDE-47 and human health, few reports were related to breast carcinoma. In the present study, the toxicity mechanism of BDE-47 was investigated by using MCF-7 breast cancer cells. Metabolomics analysis was conducted by using ultra-high performance liquid chromatography coupled with mass spectrometry (UHPLC-MS). Results showed that the toxicity to MCF-7 cells gradually increased when the concentration of BDE-47 exceeded 1 muM in the medium with 1% fetal bovine serum (FBS). It was found that pyrimidine metabolism, purine metabolism and pentose phosphate pathway (PPP) were the most influenced metabolic pathways, and the metabolites in the three metabolic pathways were significantly downregulated. Moreover, the increase of reactive oxygen species (ROS) was detected by using the 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) staining method. The obtained results suggested that the BDE-47 induced oxidative stress by downregulating the NADPH generation in PPP. The pyrimidine metabolism and purine metabolism might be downregulated by the downregulation of mRNA transcripts. Therefore, BDE-47 could induce oxidative stress by inhibiting PPP and disorder the metabolism of the entire cell subsequently. This research provided evidence for investigating mechanism of the adverse effect of BDE-47 on human health. CI - Copyright (c) 2017 Elsevier Ltd. All rights reserved. FAU - Wei, Juntong AU - Wei J AD - State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong Special Administrative Region. FAU - Xiang, Li AU - Xiang L AD - State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong Special Administrative Region. FAU - Yuan, Zigao AU - Yuan Z AD - Key Laboratory of Metabolomics at Shenzhen, Graduate School at Shenzhen, Tsinghua University, Shenzhen, China. FAU - Li, Shangfu AU - Li S AD - Key Laboratory of Metabolomics at Shenzhen, Graduate School at Shenzhen, Tsinghua University, Shenzhen, China. FAU - Yang, Chunxue AU - Yang C AD - State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong Special Administrative Region. FAU - Liu, Hongxia AU - Liu H AD - Key Laboratory of Metabolomics at Shenzhen, Graduate School at Shenzhen, Tsinghua University, Shenzhen, China. FAU - Jiang, Yuyang AU - Jiang Y AD - Key Laboratory of Metabolomics at Shenzhen, Graduate School at Shenzhen, Tsinghua University, Shenzhen, China. FAU - Cai, Zongwei AU - Cai Z AD - State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong Special Administrative Region. Electronic address: zwcai@hkbu.edu.hk. LA - eng PT - Journal Article DEP - 20171031 PL - England TA - Chemosphere JT - Chemosphere JID - 0320657 RN - 0 (Halogenated Diphenyl Ethers) RN - 0 (Reactive Oxygen Species) RN - 0F5N573A2Y (Ether) RN - 0N97R5X10X (2,2',4,4'-tetrabromodiphenyl ether) SB - IM MH - Breast Neoplasms/pathology MH - Ether MH - Halogenated Diphenyl Ethers/metabolism/*toxicity MH - Humans MH - MCF-7 Cells MH - Mass Spectrometry MH - Metabolic Networks and Pathways/drug effects MH - Metabolomics/methods MH - Oxidative Stress/drug effects MH - Reactive Oxygen Species/metabolism OTO - NOTNLM OT - BDE-47 OT - Breast cancer OT - Metabolomics OT - NADPH OT - ROS EDAT- 2017/11/09 06:00 MHDA- 2018/02/13 06:00 CRDT- 2017/11/09 06:00 PHST- 2017/08/19 00:00 [received] PHST- 2017/10/25 00:00 [revised] PHST- 2017/10/30 00:00 [accepted] PHST- 2017/11/09 06:00 [pubmed] PHST- 2018/02/13 06:00 [medline] PHST- 2017/11/09 06:00 [entrez] AID - S0045-6535(17)31756-3 [pii] AID - 10.1016/j.chemosphere.2017.10.170 [doi] PST - ppublish SO - Chemosphere. 2018 Feb;192:297-304. doi: 10.1016/j.chemosphere.2017.10.170. Epub 2017 Oct 31.