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首页> 外文期刊>Environmental Science & Technology >Mechanisms of Toxicity of Hydroxylated Polybrominated Diphenyl Ethers (HO-PBDEs) Determined by Toxicogenomic Analysis with a Live Cell Array Coupled with Mutagenesis in Escherichia coli
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Mechanisms of Toxicity of Hydroxylated Polybrominated Diphenyl Ethers (HO-PBDEs) Determined by Toxicogenomic Analysis with a Live Cell Array Coupled with Mutagenesis in Escherichia coli

机译:用活细胞阵列结合诱变作用在大肠杆菌中通过毒理基因组分析确定羟化多溴联苯醚(HO-PBDEs)的毒性机理

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摘要

Results of previous studies have indicated that 6-HO-BDE-47, the addition of the hydroxyl (HO) group to the backbone of BDE-47, significantly increased the toxicity of the chemical compared to its postulated precursor analogues, BDE-47 and 6-MeO-BDE-47. However, whether such a result is conserved across polybrominated diphenyl ether (PBDE) congeners was unknown. Here, cytotoxicity of 32 PBDE analogues (17 HO-PBDEs and 15 MeO-PBDEs) was further tested and the underlying molecular mechanism was investigated. A total of 14 of the 17 HO-PBDEs inhibited growth of Escherichia coli during 4 or 24 h durations of exposure, but none of the MeO-PBDEs was cytotoxic at the concentrations tested. 6-HO-BDE-47 and 2-HO-BDE-28 were most potent with 4 h median effect concentrations (EC_(50)) of 12.13 and 6.25 mg/L, respectively, which trended to be lesser with a longer exposure time (24 h). Expression of 30 modulated and validated genes by 6-HO-BDE-47 in a previous study was also observed after exposure to or HO-PBDE analogues. For instance, uhpT was upregulated by 13 HO-PBDEs, and three rRNA operons (rrnA, rrnB, and rrnC) were downregulated by 8 HO-PBDEs. These unanimous responses suggested a potential common molecular signaling modulated by HO-PBDEs. To explore new information on mechanisms of action, this work was extended by testing the increased susceptibility of 182 mutations of transcriptional factors (TFs) and 22 mutations as genes modulated by 6-HO-BDE-47 after exposure to 6-HO-BDE-47 at the 4 h IC_(50) concentration. Although a unanimous upregus upregulation of uhpT was observed after exposure to HO-PBDEs, no significant shift in sensitivity was observed in uhpT-defectitve mutants. The 54 genes, selected by cut-oft of 0.35 and 0.65, were determined to be responsible for "organic acid/oxoacid/carboxylic acid metabolic process" pathways, which supported a previous finding.
机译:先前的研究结果表明,与BDE-47假定的前体类似物BDE-47和BDE-47相比,在BDE-47的主链上添加羟基(HO)基团的6-HO-BDE-47大大增加了该化合物的毒性。 6-MeO-BDE-47。但是,这种结果是否在多溴二苯醚(PBDE)同源物中得以保留尚不清楚。在这里,进一步测试了32种PBDE类似物(17种HO-PBDEs和15种MeO-PBDEs)的细胞毒性,并研究了潜在的分子机制。在暴露的4或24小时内,总共17种HO-PBDEs中有14种抑制了大肠杆菌的生长,但是在所测试的浓度下,MeO-PBDEs都不具有细胞毒性。 6-HO-BDE-47和2-HO-BDE-28最有效,其4小时中位效应浓度(EC_(50))分别为12.13和6.25 mg / L,随着暴露时间的延长,其趋向于降低(24小时)。在接触HO-PBDE类似物后,在先前的研究中还观察到了6-HO-BDE-47表达的30个经过调制和验证的基因。例如,uhpT被13种HO-PBDEs上调,而三个rRNA操纵子(rrnA,rrnB和rrnC)被8种HO-PBDEs下调。这些一致的反应表明,HO-PBDEs调节了潜在的常见分子信号传导。为探索有关作用机制的新信息,通过测试暴露于6-HO-BDE-47后由182-BDE-47调节的182个转录因子(TF)突变和22个突变的敏感性增加,扩展了这项工作。在4 h IC_(50)浓度下为47。尽管在暴露于HO-PBDEs后观察到uhpT的一致上调上调,但是在uhpT缺陷型突变体中未观察到敏感性的显着变化。确定为截止值为0.35和0.65的54个基因与“有机酸/草酸/羧酸代谢过程”途径有关,这支持了先前的发现。

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  • 来源
    《Environmental Science & Technology》 |2014年第10期|5929-5937|共9页
  • 作者单位

    State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210089, People's Republic of China;

    State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210089, People's Republic of China;

    State Key Laboratory in Marine Pollution, Department of Biology and Chemistry, City University of Hong Kong, Kowloon, Hong Kong, Special Administrative Region (SAR), People's Republic of China;

    State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210089, People's Republic of China,State Key Laboratory in Marine Pollution, Department of Biology and Chemistry, City University of Hong Kong, Kowloon, Hong Kong, Special Administrative Region (SAR), People's Republic of China,Department of Biomedical Veterinary Sciences and Toxicology Centre, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5B3, Canada,Department of Zoology and Center for Integrative Toxicology, Michigan State University, East Lansing, Michigan 48824, United States;

    State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210089, People's Republic of China;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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