Is chemosensitisation by environmental pollutants ecotoxicologically relevant?

Kurth, Denise; Brack, Werner; Luckenbach, Till

doi:10.1016/j.aquatox.2015.07.017

Cited by 15 publications

(15 citation statements)

References 69 publications

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“…ABC transporters have also been shown to be actively involved in the excretion of polycyclic aromatic hydrocarbons from a range of organisms (Alharbi et al, 2016 ; Bard, 2000 ). However, a variety of chemicals and metabolites can inhibit members of the ABC superfamily of transporter proteins (Kurth et al, 2015 ; Smital & Kurelec, 1997 ) including OSPW (and the potential NAs therein) (Alharbi et al, 2016 ). We postulate that ABC transporter inhibition occurs as a stress response following NA exposure, thus protecting the cell from NA toxic effects.…”

Section: Resultsmentioning

confidence: 99%

Differential protein expression during growth on model and commercial mixtures of naphthenic acids in Pseudomonas fluorescens Pf‐5

et al. 2021

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Naphthenic acids (NAs) are carboxylic acids with the formula (C n H 2n + Z O 2 ) and are among the most toxic, persistent constituents of oil sands process‐affected waters (OSPW), produced during oil sands extraction. Currently, the proteins and mechanisms involved in NA biodegradation are unknown. Using LC‐MS/MS shotgun proteomics, we identified proteins overexpressed during the growth of Pseudomonas fluorescens Pf‐5 on a model NA (4′‐ n ‐butylphenyl)‐4‐butanoic acid ( n ‐BPBA) and commercial NA mixture (Acros). By day 11, >95% of n ‐BPBA was degraded. With Acros, a 17% reduction in intensity occurred with 10–18 carbon compounds of the Z family −2 to −14 (major NA species in this mixture). A total of 554 proteins ( n ‐BPBA) and 631 proteins (Acros) were overexpressed during growth on NAs, including several transporters (e.g., ABC transporters), suggesting a cellular protective response from NA toxicity. Several proteins associated with fatty acid, lipid, and amino acid metabolism were also overexpressed, including acyl‐CoA dehydrogenase and acyl‐CoA thioesterase II, which catalyze part of the fatty acid beta‐oxidation pathway. Indeed, multiple enzymes involved in the fatty acid oxidation pathway were upregulated. Given the presumed structural similarity between alkyl‐carboxylic acid side chains and fatty acids, we postulate that P . fluorescens Pf‐5 was using existing fatty acid catabolic pathways (among others) during NA degradation.

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Section: Resultsmentioning

confidence: 99%

Differential protein expression during growth on model and commercial mixtures of naphthenic acids in Pseudomonas fluorescens Pf‐5

et al. 2021

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“…Among the major contributors to the total pollutant levels were the compounds that we previously identified as inhibitors of an important cell defense protein ( Nicklisch et al 2016 ). Transporters have already been demonstrated to be important proteins in determining the uptake of hydrophobic xenobiotics such as pharmaceuticals into the human body ( Ambudkar et al 1999 ; International Transporter Consortium et al 2010 ; Leslie et al 2005 ), and they may be equally important for understanding the behavior of environmental chemicals in humans and other animals ( Epel et al 2008 ; Kurelec 1992 , 1997 ; Kurth et al 2015 ; Smital et al 2004 ). The observation that some persistent organic pollutant congeners could act as inhibitors of these proteins suggests that real world pollutant mixtures, containing high levels of TICs, might act to enhance the accumulation of chemicals that would otherwise be eliminated.…”

Section: Discussionmentioning

confidence: 99%

Geographic Differences in Persistent Organic Pollutant Levels of Yellowfin Tuna

Nicklisch

Bonito

Sandin

et al. 2017

Environ Health Perspect

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Background:Fish are a source of persistent organic pollutants (POPs) in the human diet. Although species, trophic level, and means of production are typically considered in predicting fish pollutant load, and thus recommendations of consumption, capture location is usually not accounted for.Objectives:Yellowfin tuna (Thunnus albacares) are harvested from across the world’s oceans and are widely consumed. Here, we determined geographic variation in the overall mass, concentration, and composition of POPs in yellowfin and examined the differences in levels of several POP congeners of potential relevance to human health.Methods:We sampled dorsal muscle of 117 yellowfin tuna from 12 locations worldwide, and measured POP levels using combined liquid or gas chromatography and mass spectrometry according to U.S. Environmental Protection Agency standard procedures.Results:POP levels varied significantly among sites, more than 36-fold on a mass basis. Individual fish levels ranged from 0.16 to 138.29ng/g wet weight and lipid-normalized concentrations from 0.1 to 12.7μM. Levels of 10 congeners that interfere with the cellular defense protein P-glycoprotein, termed transporter interfering compounds (TICs), ranged from 0.05 to 35.03ng/g wet weight and from 0.03 to 3.32μM in tuna lipid. Levels of TICs, and their individual congeners, were strongly associated with the overall POP load. Risk-based analysis of several carcinogenic POPs indicated that the fish with the highest levels of these potentially harmful compounds were clustered at specific geographic locations.Conclusions:Capture location is an important consideration when assessing the level and risk of human exposure to POPs through ingestion of wild fish. https://doi.org/10.1289/EHP518

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“…Therefore, there is the potential for compounds that might otherwise be considered as not posing a threat to the health of organisms to cause adverse effects, particularly when they occur as part of complex mixtures with toxic compounds that are substrates of ABC proteins (Epel et al ., ; Kurelec, ). Although numerous chemicals are chemosensitizers, whether chemosensitization is a mechanism of toxicity at environmentally relevant concentrations of chemicals is not known (reviewed in Kurth et al ., ).…”

Section: Introductionmentioning

confidence: 97%

“…For example, multidrug resistance proteins (MRPs), which are members of the ABC superfamily of proteins, remove glutathione‐conjugated metabolites of PAHs from cells (Hessel et al ., ; Kranz et al ., ). However, numerous chemicals that are structurally diverse can competitively or non‐competitively inhibit activity of ABC transporters, causing greater bioaccumulation of substrates of ABC transporters and greater sensitivity to these substrates, a phenomenon known as chemosensitization (Kurelec, ; Kurth et al ., ; Luckenbach et al ., ). Therefore, there is the potential for compounds that might otherwise be considered as not posing a threat to the health of organisms to cause adverse effects, particularly when they occur as part of complex mixtures with toxic compounds that are substrates of ABC proteins (Epel et al ., ; Kurelec, ).…”

Section: Introductionmentioning

confidence: 99%

Toxicokinetics and toxicodynamics of chlorpyrifos is altered in embryos of Japanese medaka exposed to oil sands process‐affected water: evidence for inhibition of P‐glycoprotein

Alharbi

Alcorn

Almousa

et al. 2016

J of Applied Toxicology

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Oil sands process-affected water (OSPW) is generated during extraction of bitumen in the surface mining oil sands industry in Alberta, Canada. Studies were performed in vitro by use of Caco-2 cells, and in vivo with larvae of Japanese medaka (Oryzias latipes) to determine if organic compounds from the aqueous phase of OSPW inhibit ATP binding cassette protein ABCB1 (permeability-glycoprotein, P-gp). Neutral and basic fractions of OSPW inhibited activity of P-gp in Caco-2 cells by 1.9- and 2.0-fold, respectively, while the acidic fraction had the least effect. The organophosphate pesticides chlorpyrifos (a substrate of P-gp) and malathion (not a substrate of P-gp), were used as model chemicals to investigate inhibition of P-gp in larvae. Co-exposure to chlorpyrifos and an extract of OSPW containing basic and neutral compounds reduced survival of larvae to 26.5% compared to survival of larvae exposed only to chlorpyrifos, which was 93.7%. However, co-exposure to malathion and the extract of OSPW did not cause acute lethality compared to exposure only to malathion. Accumulation and bioconcentration of chlorpyrifos, but not malathion, was greater in larvae co-exposed with the extract of OSPW. The terminal elimination half-life of chlorpyrifos in larvae exposed to chlorpyrifos in freshwater was 5 days compared with 11.3 days in larvae exposed to chlorpyrifos in OSPW. Results suggest that in non-acute exposures, basic and neutral organic compounds in the water-soluble fraction of OSPW inhibit activity of P-gp, which suggests that OSPW has the potential to cause adverse effects by chemosensitization. Copyright © 2016 John Wiley & Sons, Ltd.

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Is chemosensitisation by environmental pollutants ecotoxicologically relevant?

Cited by 15 publications

References 69 publications

Differential protein expression during growth on model and commercial mixtures of naphthenic acids in Pseudomonas fluorescens Pf‐5

Differential protein expression during growth on model and commercial mixtures of naphthenic acids in Pseudomonas fluorescens Pf‐5

Geographic Differences in Persistent Organic Pollutant Levels of Yellowfin Tuna

Toxicokinetics and toxicodynamics of chlorpyrifos is altered in embryos of Japanese medaka exposed to oil sands process‐affected water: evidence for inhibition of P‐glycoprotein

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