Activation of AhR-mediated toxicity pathway by emerging pollutants polychlorinated diphenyl sulfides

Junjiang Zhang; Xiaowei Zhang; Pu Xia; Rui Zhang; Yang Wu; Jie Xia; Guanyong Su; Jiamin Zhang; John P. Giesy; Zunyao Wang; Daniel L. Villeneuve; Hongxia Yu

doi:10.1016/j.chemosphere.2015.09.107

Activation of AhR-mediated toxicity pathway by emerging pollutants polychlorinated diphenyl sulfides

Junjiang Zhang, Xiaowei Zhang^*, Pu Xia, Rui Zhang, Yang Wu, Jie Xia, Guanyong Su, Jiamin Zhang, John P. Giesy, Zunyao Wang, Daniel L. Villeneuve, Hongxia Yu

^*Corresponding author for this work

Biosciences

Research output: Contribution to journal › Article › peer-review

Abstract

Polychlorinated diphenyl sulfides (PCDPSs) are a group of environmental pollutants for which limited toxicological information is available. This study tested the hypothesis that PCDPSs could activate the mammalian aryl hydrocarbon receptor (AhR) mediated toxicity pathways. Eighteen PCDPSs were tested in the H4IIE-. luc transactivation assay, with 13/18 causing concentration-dependent AhR activation. Potencies of several congeners were similar to those of mono-. ortho substituted polychlorinated biphenyls. A RNA sequencing (RNA-seq)-based transcriptomic analysis was performed on H4IIE cells treated with two PCDPS congeners, 2,2',3,3',4,5,6-hepta-CDPS, and 2,4,4',5-tetra-CDPS. Results of RNA-seq revealed a remarkable modulation on a relatively short gene list by exposure to the tested concentrations of PCDPSs, among which, Cyp1 responded with the greatest fold up-regulation. Both the identities of the modulated transcripts and the associated pathways were consistent with targets and pathways known to be modulated by other types of AhR agonists and there was little evidence for significant off-target effects within the cellular context of the H4IIE bioassay. The results suggest AhR activation as a toxicologically relevant mode of action for PCDPSs suggests the utility of AhR-related toxicity pathways for predicting potential hazards associated with PCDPS exposure in mammals and potentially other vertebrates.

Original language	English
Pages (from-to)	1754-1762
Number of pages	9
Journal	Chemosphere
Volume	144
DOIs	https://doi.org/10.1016/j.chemosphere.2015.09.107
Publication status	Published - 1 Feb 2016

Bibliographical note

Funding Information:
This work was supported by the National Natural Science Foundation of China (Grant No. 21322704 and 21007025 ), National High-tech R&D Program of China (863 Program, Grant No. 2013AA06A309 ). The research is also supported by the Collaborative Innovation Center for Regional Environmental Quality . Dr. Daniel L Villeneuve and Dr. John Giesy were supported by the program of 2014 “High Level Foreign Experts” (# GDT20143200016 ) of the State Administration of Foreign Experts Affairs , the P.R. China. Dr. John Giesy was also supported by the Einstein Professor Program of the Chinese Academy of Sciences and by the Canada Research Chair program .

Publisher Copyright:
© 2015 Elsevier Ltd.

Keywords

Cyp1A
Ligand binding domain
Molecular initiating event
RNA-seq
Toxicogenomics
Xenobiotic metabolism

ASJC Scopus subject areas

Environmental Engineering
Environmental Chemistry
General Chemistry
Pollution
Public Health, Environmental and Occupational Health
Health, Toxicology and Mutagenesis

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.chemosphere.2015.09.107

Cite this

@article{8fd43c31c5d74af4a0e0e4bec363aa1a,

title = "Activation of AhR-mediated toxicity pathway by emerging pollutants polychlorinated diphenyl sulfides",

abstract = "Polychlorinated diphenyl sulfides (PCDPSs) are a group of environmental pollutants for which limited toxicological information is available. This study tested the hypothesis that PCDPSs could activate the mammalian aryl hydrocarbon receptor (AhR) mediated toxicity pathways. Eighteen PCDPSs were tested in the H4IIE-. luc transactivation assay, with 13/18 causing concentration-dependent AhR activation. Potencies of several congeners were similar to those of mono-. ortho substituted polychlorinated biphenyls. A RNA sequencing (RNA-seq)-based transcriptomic analysis was performed on H4IIE cells treated with two PCDPS congeners, 2,2',3,3',4,5,6-hepta-CDPS, and 2,4,4',5-tetra-CDPS. Results of RNA-seq revealed a remarkable modulation on a relatively short gene list by exposure to the tested concentrations of PCDPSs, among which, Cyp1 responded with the greatest fold up-regulation. Both the identities of the modulated transcripts and the associated pathways were consistent with targets and pathways known to be modulated by other types of AhR agonists and there was little evidence for significant off-target effects within the cellular context of the H4IIE bioassay. The results suggest AhR activation as a toxicologically relevant mode of action for PCDPSs suggests the utility of AhR-related toxicity pathways for predicting potential hazards associated with PCDPS exposure in mammals and potentially other vertebrates.",

keywords = "Cyp1A, Ligand binding domain, Molecular initiating event, RNA-seq, Toxicogenomics, Xenobiotic metabolism",

author = "Junjiang Zhang and Xiaowei Zhang and Pu Xia and Rui Zhang and Yang Wu and Jie Xia and Guanyong Su and Jiamin Zhang and Giesy, {John P.} and Zunyao Wang and Villeneuve, {Daniel L.} and Hongxia Yu",

note = "Funding Information: This work was supported by the National Natural Science Foundation of China (Grant No. 21322704 and 21007025 ), National High-tech R&D Program of China (863 Program, Grant No. 2013AA06A309 ). The research is also supported by the Collaborative Innovation Center for Regional Environmental Quality . Dr. Daniel L Villeneuve and Dr. John Giesy were supported by the program of 2014 “High Level Foreign Experts” (# GDT20143200016 ) of the State Administration of Foreign Experts Affairs , the P.R. China. Dr. John Giesy was also supported by the Einstein Professor Program of the Chinese Academy of Sciences and by the Canada Research Chair program . Publisher Copyright: {\textcopyright} 2015 Elsevier Ltd.",

year = "2016",

month = feb,

day = "1",

doi = "10.1016/j.chemosphere.2015.09.107",

language = "English",

volume = "144",

pages = "1754--1762",

journal = "Chemosphere",

issn = "0045-6535",

publisher = "Elsevier",

}

TY - JOUR

T1 - Activation of AhR-mediated toxicity pathway by emerging pollutants polychlorinated diphenyl sulfides

AU - Zhang, Junjiang

AU - Zhang, Xiaowei

AU - Xia, Pu

AU - Zhang, Rui

AU - Wu, Yang

AU - Xia, Jie

AU - Su, Guanyong

AU - Zhang, Jiamin

AU - Giesy, John P.

AU - Wang, Zunyao

AU - Villeneuve, Daniel L.

AU - Yu, Hongxia

N1 - Funding Information: This work was supported by the National Natural Science Foundation of China (Grant No. 21322704 and 21007025 ), National High-tech R&D Program of China (863 Program, Grant No. 2013AA06A309 ). The research is also supported by the Collaborative Innovation Center for Regional Environmental Quality . Dr. Daniel L Villeneuve and Dr. John Giesy were supported by the program of 2014 “High Level Foreign Experts” (# GDT20143200016 ) of the State Administration of Foreign Experts Affairs , the P.R. China. Dr. John Giesy was also supported by the Einstein Professor Program of the Chinese Academy of Sciences and by the Canada Research Chair program . Publisher Copyright: © 2015 Elsevier Ltd.

PY - 2016/2/1

Y1 - 2016/2/1

N2 - Polychlorinated diphenyl sulfides (PCDPSs) are a group of environmental pollutants for which limited toxicological information is available. This study tested the hypothesis that PCDPSs could activate the mammalian aryl hydrocarbon receptor (AhR) mediated toxicity pathways. Eighteen PCDPSs were tested in the H4IIE-. luc transactivation assay, with 13/18 causing concentration-dependent AhR activation. Potencies of several congeners were similar to those of mono-. ortho substituted polychlorinated biphenyls. A RNA sequencing (RNA-seq)-based transcriptomic analysis was performed on H4IIE cells treated with two PCDPS congeners, 2,2',3,3',4,5,6-hepta-CDPS, and 2,4,4',5-tetra-CDPS. Results of RNA-seq revealed a remarkable modulation on a relatively short gene list by exposure to the tested concentrations of PCDPSs, among which, Cyp1 responded with the greatest fold up-regulation. Both the identities of the modulated transcripts and the associated pathways were consistent with targets and pathways known to be modulated by other types of AhR agonists and there was little evidence for significant off-target effects within the cellular context of the H4IIE bioassay. The results suggest AhR activation as a toxicologically relevant mode of action for PCDPSs suggests the utility of AhR-related toxicity pathways for predicting potential hazards associated with PCDPS exposure in mammals and potentially other vertebrates.

AB - Polychlorinated diphenyl sulfides (PCDPSs) are a group of environmental pollutants for which limited toxicological information is available. This study tested the hypothesis that PCDPSs could activate the mammalian aryl hydrocarbon receptor (AhR) mediated toxicity pathways. Eighteen PCDPSs were tested in the H4IIE-. luc transactivation assay, with 13/18 causing concentration-dependent AhR activation. Potencies of several congeners were similar to those of mono-. ortho substituted polychlorinated biphenyls. A RNA sequencing (RNA-seq)-based transcriptomic analysis was performed on H4IIE cells treated with two PCDPS congeners, 2,2',3,3',4,5,6-hepta-CDPS, and 2,4,4',5-tetra-CDPS. Results of RNA-seq revealed a remarkable modulation on a relatively short gene list by exposure to the tested concentrations of PCDPSs, among which, Cyp1 responded with the greatest fold up-regulation. Both the identities of the modulated transcripts and the associated pathways were consistent with targets and pathways known to be modulated by other types of AhR agonists and there was little evidence for significant off-target effects within the cellular context of the H4IIE bioassay. The results suggest AhR activation as a toxicologically relevant mode of action for PCDPSs suggests the utility of AhR-related toxicity pathways for predicting potential hazards associated with PCDPS exposure in mammals and potentially other vertebrates.

KW - Cyp1A

KW - Ligand binding domain

KW - Molecular initiating event

KW - RNA-seq

KW - Toxicogenomics

KW - Xenobiotic metabolism

UR - http://www.scopus.com/inward/record.url?scp=84952895150&partnerID=8YFLogxK

U2 - 10.1016/j.chemosphere.2015.09.107

DO - 10.1016/j.chemosphere.2015.09.107

M3 - Article

C2 - 26524144

AN - SCOPUS:84952895150

SN - 0045-6535

VL - 144

SP - 1754

EP - 1762

JO - Chemosphere

JF - Chemosphere

ER -

Activation of AhR-mediated toxicity pathway by emerging pollutants polychlorinated diphenyl sulfides

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Fingerprint

Cite this