Assessing the receptor-mediated activity of PAHs using AhR-, ERα- and PPARγ- CALUX bioassays

Boonen, Imke; Heyst, Annelies Van; Langenhove, Kersten Van; Hoeck, Els Van; Mertens, Birgit; Denison, Michael S.; Elskens, Marc; Demaegdt, Heidi

doi:10.1016/j.fct.2020.111602

Cited by 30 publications

(20 citation statements)

References 48 publications

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“…BaP, fluoranthene) present in the RM (Mix14, Mix19, Mix14NWL and Mix19NWL) inhibit the expression of vtg and erα genes by acting through the AhR. This is very likely to happen for BaP but not for fluoranthene, which did not induce AhR response in PLHC-1 cells ( Louiz et al, 2008 ) and resulted a very weak AhR activator in PAH-CALUX ( Boonen et al, 2020 ). Regarding the ER-AhR cross-talk mechanism, it also occurs in the cell systems used in this study as AhR is expressed in most of the cell lines.…”

Section: Discussionmentioning

confidence: 99%

Estrogenicity of chemical mixtures revealed by a panel of bioassays

Gómez

Niegowska

Navarro

et al. 2021

Science of The Total Environment

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Estrogenic compounds are widely released to surface waters and may cause adverse effects to sensitive aquatic species. Three hormones, estrone, 17β-estradiol and 17α-ethinylestradiol, are of particular concern as they are bioactive at very low concentrations. Current analytical methods are not all sensitive enough for monitoring these substances in water and do not cover mixture effects. Bioassays could complement chemical analysis since they detect the overall effect of complex mixtures. Here, four chemical mixtures and two hormone mixtures were prepared and tested as reference materials together with two environmental water samples by eight laboratories employing nine in vitro and in vivo bioassays covering different steps involved in the estrogenic response. The reference materials included priority substances under the European Water Framework Directive, hormones and other emerging pollutants. Each substance in the mixture was present at its proposed safety limit concentration (EQS) in the European legislation. The in vitro bioassays detected the estrogenic effect of chemical mixtures even when 17β-estradiol was not present but differences in responsiveness were observed. LiBERA was the most responsive, followed by LYES. The additive effect of the hormones was captured by ERα-CALUX, MELN, LYES and LiBERA. Particularly, all in vitro bioassays detected the estrogenic effects in environmental water samples (EEQ values in the range of 0.75–304 × EQS), although the concentrations of hormones were below the limit of quantification in analytical measurements. The present study confirms the applicability of reference materials for estrogenic effects' detection through bioassays and indicates possible methodological drawbacks of some of them that may lead to false negative/positive outcomes. The observed difference in responsiveness among bioassays – based on mixture composition - is probably due to biological differences between them, suggesting that panels of bioassays with different characteristics should be applied according to specific environmental pollution conditions.

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Section: Discussionmentioning

confidence: 99%

Estrogenicity of chemical mixtures revealed by a panel of bioassays

Gómez

Niegowska

Navarro

et al. 2021

Science of The Total Environment

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“…This was most obvious for hickory sample 2, where the non-extracted sample had the highest efficacy of all tested liquid smoke samples, and the activity was drastically reduced after SPE extraction. AhR activity can be induced by numerous chemicals, for example by PAHs (Boonen et al 2020 ).…”

Section: Discussionmentioning

confidence: 99%

“…However, higher concentrations could be tested than of the non-extracted samples due to cytotoxicity, and seven of the SPE samples exhibited estrogenic activities. Boonen et al ( 2020 ) reported ER activity by BaP in bioassays. No AR activities, agonistic or antagonistic, were detected in the non-extracted samples, while two of the SPE samples were active in the highest concentration.…”

Section: Discussionmentioning

confidence: 99%

An in vitro-based hazard assessment of liquid smoke food flavourings

et al. 2021

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Liquid smoke products are widely used as a food additive to create a desired smoke flavour. These products may contain hazardous chemicals generated during the wood-burning process. However, the toxic effects of these types of hazardous chemicals constituting in the commercially available products are largely unknown. Therefore, a test battery of cell-based in vitro methods, covering different modes of actions of high relevance to human health, was applied to study liquid smoke products. Ten liquid smoke flavourings were tested as non-extracted and extracted. To assess the potential drivers of toxicity, we used two different solvents. The battery of in vitro methods covered estrogenicity, androgenicity, oxidative stress, aryl hydrocarbon receptor activity and genotoxicity. The non-extracted samples were tested at concentrations 0.002 to 1 μL liquid smoke flavouring/mL culture medium, while extracted samples were tested from 0.003 to 200 μL/mL. Genotoxicity was observed for nearly all non-extracted and all hexane-extracted samples, in which the former had higher potency. No genotoxicity was observed for ethyl acetate-extracted samples. Oxidative stress was activated by almost all extracted and non-extracted samples, while approximately half of the samples had aryl hydrocarbon receptor and estrogen receptor activities. This study used effect-based methods to evaluate the complex mixtures of liquid smoke flavourings. The increased bioactivities seen upon extractions indicate that non-polar chemicals are driving the genotoxicity, while polar substances are increasing oxidative stress and cytotoxic responses. The differences in responses indicate that non-extracted products contain chemicals that are able to antagonize toxic effects, and upon extraction, the protective substances are lost.

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“…AHR is now considered as an endocrine disruptor target like other EATS receptors ( Tq et al, 2020 ); despite this knowledge, much remains unknown about the link between AHR-elicited gene expression and metabolic impairments, and cell-based bioassays are needed to highlight potential metabolic disruptors acting through AHR binding. In this way, luciferase reporter gene assays for AHR have been developed for chemical screening and have proven their efficacy to detect potential AHR activators in environmental mixture ( Boonen et al, 2020 ).…”

Section: Non-eats Modalities Of Concern For Hormonally Active Agentsmentioning

confidence: 99%