Hydroxylated polychlorinated biphenyls increase reactive oxygen species formation and induce cell death in cultured cerebellar granule cells

Anne Dreiem; Sidsel Rykken; Hans-Joachim Lehmler; Larry W Robertson; Frode Fonnum

doi:10.1016/j.taap.2009.07.016

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Hydroxylated polychlorinated biphenyls increase reactive oxygen species formation and induce cell death in cultured cerebellar granule cells

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Hydroxylated polychlorinated biphenyls increase reactive oxygen species formation and induce cell death in cultured cerebellar granule cells

Anne Dreiem, Sidsel Rykken, Hans-Joachim Lehmler, Larry W Robertson and Frode Fonnum

Toxicology and applied pharmacology, Vol.240(2), pp.306-313

2009

DOI: 10.1016/j.taap.2009.07.016

PMCID: PMC2753730

PMID: 19631230

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Abstract

Polychlorinated biphenyls (PCBs) are persistent organic pollutants that bioaccumulate in the body, however, they can be metabolized to more water-soluble products. Although they are more readily excreted than the parent compounds, some of the metabolites are still hydrophobic and may be more available to target tissues, such as the brain. They can also cross the placenta and reach a developing foetus. Much less is known about the toxicity of PCB metabolites than about the parent compounds. In the present study, we have investigated the effects of eight hydroxylated (OH) PCB congeners (2′-OH PCB 3, 4-OH PCB 14, 4-OH PCB 34, 4′-OH PCB 35, 4-OH PCB 36, 4′-OH PCB 36, 4-OH PCB 39, and 4′-OH PCB 68) on reactive oxygen species (ROS) formation and cell viability in rat cerebellar granule cells. We found that, similar to their parent compounds, OH-PCBs are potent ROS inducers with potency 4-OH PCB 14 < 4-OH PCB 36 < 4-OH PCB 34 < 4′-OH PCB 36 < 4′-OH PCB 68 < 4-OH PCB 39 < 4′-OH PCB 35. 4-OH PCB 36 was the most potent cell death inducer, and caused apoptotic or necrotic morphology depending on concentration. Inhibition of ERK1/2 kinase with U0126 reduced both cell death and ROS formation, suggesting that ERK1/2 activation is involved in OH-PCB toxicity. The results indicate that the hydroxylation of PCBs may not constitute a detoxification reaction. Since OH-PCBs like their parent compounds are retained in the body and may be more widely distributed to sensitive tissues, it is important that not only the levels of the parent compounds but also the levels of their metabolites are taken into account during risk assessment of PCBs and related compounds.

PCBs

ERK1/2

Reactive oxygen species

Hydroxylated PCBs

Cell death

Cerebellar granule cells

Cell toxicity

Details

Title: Subtitle: Hydroxylated polychlorinated biphenyls increase reactive oxygen species formation and induce cell death in cultured cerebellar granule cells
Creators: Anne Dreiem - Department of Biochemistry, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
Sidsel Rykken - Norwegian Defence Research Establishment, Department for Protection, Kjeller, Norway
Hans-Joachim Lehmler - Department of Occupational and Environmental Health, University of Iowa, Iowa, USA
Larry W Robertson - Department of Occupational and Environmental Health, University of Iowa, Iowa, USA
Frode Fonnum - Department of Biochemistry, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
Resource Type: Journal article
Publication Details: Toxicology and applied pharmacology, Vol.240(2), pp.306-313
DOI: 10.1016/j.taap.2009.07.016
PMID: 19631230
PMCID: PMC2753730
NLM abbreviation: Toxicol Appl Pharmacol
ISSN: 0041-008X
eISSN: 1096-0333
Publisher: Elsevier Inc
Language: English
Date published: 2009
Academic Unit: Occupational and Environmental Health; Iowa Neuroscience Institute; Iowa Superfund Research Program
Record Identifier: 9984000920602771

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