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

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

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Original languageEnglish
Pages (from-to)5929-5937
Journal / PublicationEnvironmental Science and Technology
Volume48
Issue number10
Publication statusPublished - 20 May 2014

Abstract

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 (EC50) 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 other 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 IC50 concentration. Although a unanimous upregulation of uhpT was observed after exposure to HO-PBDEs, no significant shift in sensitivity was observed in uhpT-defective mutants. The 54 genes, selected by cut-offs 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. © 2014 American Chemical Society.

Citation Format(s)

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. / Su, Guanyong; Yu, Hongxia; Lam, Michael H. W.; Giesy, John P.; Zhang, Xiaowei.

In: Environmental Science and Technology, Vol. 48, No. 10, 20.05.2014, p. 5929-5937.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review