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Cytotoxic effects of pentachlorophenol (PCP) and its metabolite tetrachlorohydroquinone (TCHQ) on liver cells are modulated by antioxidants

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Abstract

The worldwide distribution and high bioaccumulation potential of pentachlorophenol (PCP) in aquatic organisms imply a high toxicological impact in aquatic systems. Firstly, our investigations show that, similar to mammalian cell lines, PCP can be metabolized to tetrachlorohydroquinone (TCHQ) in the permanent cell line derived from rainbow trout liver cells (RTL-W1). Moreover, we demonstrate that PCP as well as its metabolite TCHQ is capable of influencing the viability of these cells. Three cell viability assays were performed to assess possible cellular targets of these substances. Thus, the cytotoxicity of the PCP-derivative TCHQ was shown for the first time in a fish cell line. Further investigations revealed the involvement of ROS in the cytotoxicity of PCP and its metabolite TCHQ. The observation of oxidative stress provides a plausible explanation for the increased cytotoxicity at higher concentrations especially for PCP and implies possible mechanisms underlying these observations. In addition, antioxidants such as ascorbic acid and quercetin modulate the detrimental effects of PCP and TCHQ whereby both compounds exacerbate the cytotoxic effects of high PCP and TCHQ concentrations.

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Abbreviations

EtOH:

Ethanol

FBS:

Fetal bovine serum

MeOH:

Methanol

NR:

Neutral red

PCP:

Pentachlorophenol

PI:

Propidium iodide

RTL-W1:

Rainbow trout liver cells

ROS:

Reactive oxygen species

SOD:

Superoxide dismutase

TCHQ:

Tetrachlorohydroquinone

MTT:

Thiazolyl blue tetrazolium bromide

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Acknowledgments

The authors owe special thanks to the Bundesamt für Umwelt, Wald und Landschaft (BUWAL) in Bern (Switzerland) for financial support of the project “MicroPoll” (project no. StoBoBio/2004.H.15a) which allowed the initial investigations on effects of PCP on RTL W-1 cells. Grateful acknowledgment is also made for the financial support by the “Fonds zur Förderung von Lehre und Forschung” that belongs to the Freiwillige Akademische Gesellschaft (FAG) in Basel (Switzerland) which enabled us to purchase the plate reader Infinite M200 from Tecan Group Ltd. (Switzerland). Furthermore, the authors like to thank Prof. Kristin Schirmer from the Swiss Federal Institute of Aquatic Science and Technology (Eawag, Dübendorf, Switzerland) for providing the liver cell line established from rainbow trout. In addition, we are grateful to Heidi Schiffer for maintaining the cell cultures and additional help in the laboratory work.

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Authors and Affiliations

  1. Institute of Natural Resource Sciences (IUNR), Zurich University of Applied Sciences (ZHAW), Gruental, P.O. Box, 8820, Waedenswil, Switzerland

    Constanze Pietsch

  2. Man–Society–Environment, Department of Environmental Sciences, University Basel, Vesalgasse 1, 4051, Basel, Switzerland

    Constanze Pietsch & Patricia Burkhardt-Holm

  3. Eawag, Swiss Federal Institute of Aquatic Science and Technology, Überlandstrasse 133, 8600, Dübendorf, Switzerland

    Juliane Hollender & Falk Dorusch

  4. Department of Biological Sciences, University of Alberta, CW 405 Biological Sciences Building, Edmonton, AB, T6G 2E9, Canada

    Patricia Burkhardt-Holm

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  1. Constanze Pietsch
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Correspondence to Constanze Pietsch.

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Pietsch, C., Hollender, J., Dorusch, F. et al. Cytotoxic effects of pentachlorophenol (PCP) and its metabolite tetrachlorohydroquinone (TCHQ) on liver cells are modulated by antioxidants. Cell Biol Toxicol 30, 233–252 (2014). https://doi.org/10.1007/s10565-014-9283-4

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