title: Toxicogenomic mechanisms of 6-HO-BDE-47, 6-MeO-BDE-47, and BDE-47 in E. coli.
abstract: Cytotoxicity of 6-HO-BDE-47 and its two analogues, BDE-47 and 6-MeO-BDE-47, and the associated molecular mechanisms were assessed by use of a live cell reporter assay system which contains a library of 1820 modified green fluorescent protein (GFP) expressing promoter reporter vectors constructed from E. coli K12 strains. 6-HO-BDE-47 inhibited growth of E. coli with a 4 h median effect concentration (EC50) of 22.52 ± 2.20 mg/L, but neither BDE-47 nor 6-MeO-BDE-47 were cytotoxic. Thus, 6-HO-BDE-47 might serve as an antibiotic in some living organisms. Exposure to 6-HO-BDE-47 resulted in 65 (fold change >2) or 129 (fold change >1.5) genes being differentially expressed. The no observed transcriptional effect concentration (NOTEC) and median transcriptional effect concentration (TEC50) based on transcriptional end points, of 6-HO-BDE-47 were 0.0438 and 0.580 mg/L, respectively. The transcriptional responses were 514- and 39-fold more sensitive than the acute EC50 to inhibit cell growth. Most of the genes that were differentially expressed in response to 6-HO-BDE-47 were not modulated by BDE-47 or 6-MeO-BDE-47. These results suggest that cytotoxicity of 6-HO-BDE-47 to E. coli was via a mechanism that was different from that of either BDE-47 or 6-MeO-BDE-47. Gene expression associated with metabolic pathways was more responsive to 6-HO-BDE-47, which suggests that this pathway might be the primary target of this compound.
authors: State Key Laboratory of Pollution Control and Resource Reuse & School of the Environment, Nanjing University, Nanjing, People's Republic of China.
authors: Guanyong
authors: G
authors: Su
authors: Xiaowei
authors: X
authors: Zhang
authors: Hongling
authors: H
authors: Liu
authors: John P
authors: JP
authors: Giesy
authors: Michael H W
authors: MH
authors: Lam
authors: Paul K S
authors: PK
authors: Lam
authors: Maqsood A
authors: MA
authors: Siddiqui
authors: Javed
authors: J
authors: Musarrat
authors: Abdulaziz
authors: A
authors: Al-Khedhairy
authors: Hongxia
authors: H
authors: Yu
mesh_terms: D000840:Anisoles / Q000633:toxicity*; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics*; D005411:Flame Retardants / Q000633:toxicity; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D055768:Halogenated Diphenyl Ethers / Q000633:toxicity*; D015394:Molecular Structure; D010636:Phenols / Q000633:toxicity*; D011075:Polybrominated Biphenyls / Q000633:toxicity*
chemical_list: C496823:2-(2',4'-dibromophenoxy)-3,5-dibromoanisole; D000840:Anisoles; D005411:Flame Retardants; D055768:Halogenated Diphenyl Ethers; D010636:Phenols; D011075:Polybrominated Biphenyls; C511295:2,2',4,4'-tetrabromodiphenyl ether; C085794:3,5-dibromo-2-(2,4-dibromophenoxy)phenol