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Article ; Online: Costs of molecular adaptation to the chemical exposome: a focus on xenobiotic metabolism pathways.

Tomkiewicz, Céline / Coumoul, Xavier / Nioche, Pierre / Barouki, Robert / Blanc, Etienne B

Philosophical transactions of the Royal Society of London. Series B, Biological sciences

2024 Volume 379, Issue 1898, Page(s) 20220510

Abstract: Organisms adapt to their environment through different pathways. In vertebrates, xenobiotics are detected, metabolized and eliminated through the inducible xenobiotic-metabolizing pathways (XMP) which can also generate reactive toxic intermediates. In ... ...

Abstract	Organisms adapt to their environment through different pathways. In vertebrates, xenobiotics are detected, metabolized and eliminated through the inducible xenobiotic-metabolizing pathways (XMP) which can also generate reactive toxic intermediates. In this review, we will discuss the impacts of the chemical exposome complexity on the balance between detoxication and side effects. There is a large discrepancy between the limited number of proteins involved in these pathways (few dozens) and the diversity and complexity of the chemical exposome (tens of thousands of chemicals). Several XMP proteins have a low specificity which allows them to bind and/or metabolize a large number of chemicals. This leads to undesired consequences, such as cross-inhibition, inefficient metabolism, release of toxic intermediates, etc. Furthermore, several XMP proteins have endogenous functions that may be disrupted upon exposure to exogenous chemicals. The gut microbiome produces a very large number of metabolites that enter the body and are part of the chemical exposome. It can metabolize xenobiotics and either eliminate them or lead to toxic derivatives. The complex interactions between chemicals of different origins will be illustrated by the diverse roles of the aryl hydrocarbon receptor which binds and transduces the signals of a large number of xenobiotics, microbiome metabolites, dietary chemicals and endogenous compounds. This article is part of the theme issue 'Endocrine responses to environmental variation: conceptual approaches and recent developments'.
MeSH term(s)	Animals ; Xenobiotics/chemistry ; Xenobiotics/metabolism ; Xenobiotics/toxicity ; Exposome ; Inactivation, Metabolic ; Receptors, Aryl Hydrocarbon/metabolism ; Gastrointestinal Microbiome
Chemical Substances	Xenobiotics ; Receptors, Aryl Hydrocarbon
Language	English
Publishing date	2024-02-05
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	208382-6
ISSN	1471-2970 ; 0080-4622 ; 0264-3839 ; 0962-8436
ISSN (online)	1471-2970
ISSN	0080-4622 ; 0264-3839 ; 0962-8436
DOI	10.1098/rstb.2022.0510
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Article ; Online: The exposome and liver disease - how environmental factors affect liver health.

Barouki, Robert / Samson, Michel / Blanc, Etienne B / Colombo, Massimo / Zucman-Rossi, Jessica / Lazaridis, Konstantinos N / Miller, Gary W / Coumoul, Xavier

Journal of hepatology

2023 Volume 79, Issue 2, Page(s) 492–505

Abstract: Since the initial development of the exposome concept, much effort has been devoted to the characterisation of the exposome through analytical, epidemiological, and toxicological/mechanistic studies. There is now an urgent need to link the exposome to ... ...

Abstract	Since the initial development of the exposome concept, much effort has been devoted to the characterisation of the exposome through analytical, epidemiological, and toxicological/mechanistic studies. There is now an urgent need to link the exposome to human diseases and to include exposomics in the characterisation of environment-linked pathologies together with genomics and other omics. Liver diseases are particularly well suited for such studies since major functions of the liver include the detection, detoxification, and elimination of xenobiotics, as well as inflammatory responses. It is well known that several liver diseases are associated with i) addictive behaviours such as alcohol consumption, smoking, and to a certain extent dietary imbalance and obesity, ii) viral and parasitic infections, and iii) exposure to toxins and occupational chemicals. Recent studies indicate that environmental exposures are also significantly associated with liver diseases, and these include air pollution (particulate matter and volatile chemicals), contaminants such as polyaromatic hydrocarbons, bisphenol A and per-and poly-fluorinated substances, and physical stressors such as radiation. Furthermore, microbial metabolites and the "gut-liver" axis play a major role in liver diseases. Exposomics is poised to play a major role in the field of liver pathology. Methodological advances such as the exposomics-metabolomics framework, the determination of risk factors' genomic and epigenomic signatures, and cross-species biological pathway analysis should further delineate the impact of the exposome on the liver, opening the way for improved prevention, as well as the identification of new biomarkers of exposure and effects, and additional therapeutic targets.
MeSH term(s)	Humans ; Exposome ; Environmental Exposure/adverse effects ; Air Pollution ; Liver Diseases/etiology
Language	English
Publishing date	2023-03-06
Publishing country	Netherlands
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	605953-3
ISSN	1600-0641 ; 0168-8278
ISSN (online)	1600-0641
ISSN	0168-8278
DOI	10.1016/j.jhep.2023.02.034
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Article ; Online: ReadEDTest: A tool to assess the readiness of in vitro test methods under development for identifying endocrine disruptors

Crouzet, Thibault / Grignard, Elise / Brion, François / Blanc, Etienne B. / Podechard, Normand / Langouet, Sophie / Alonso-Magdalena, Paloma / Hubert, Philippe / Kim, Min-ji / Audouze, Karine

Environment International. 2023 Apr., v. 174 p.107910-

2023

Abstract: Growing evidence shows that endocrine disruptors (EDs), known to affect the reproductive system, may also disturb other hormone-regulated functions leading to cancers, neurodevelopmental defects, metabolic and immune diseases. To reduce exposure to EDs ... ...

Abstract	Growing evidence shows that endocrine disruptors (EDs), known to affect the reproductive system, may also disturb other hormone-regulated functions leading to cancers, neurodevelopmental defects, metabolic and immune diseases. To reduce exposure to EDs and limit their health effects, development of screening and mechanism-based assays to identify EDs is encouraged. Nevertheless, the crucial validation step of test methods by regulatory bodies is a time- and resource-consuming process. One of the main raisons of this long duration process is that method developers, mainly researchers, are not fully aware of the regulatory needs to validate a test. We propose an online self-assessment questionnaire (SAQ) called ReadEDTest easy to be used by all researchers. The aim of ReadEDTest is to speed up the validation process by assessing readiness criteria of in vitro and fish embryo ED test methods under development. The SAQ is divided into 7 sections and 13 sub-sections containing essential information requested by the validating bodies. The readiness of the tests can be assessed by specific score limits for each sub-section. Results are displayed via a graphical representation to help identification of the sub-sections having sufficient or insufficient information. The relevance of the proposed innovative tool was supported using two test methods already validated by the OECD and four under development test methods.
Keywords	environment ; fish ; questionnaires ; reproductive system ; Endocrine disrupting chemicals ; Zebrafish embryo ; OBERON ; Pepper ; Validation process ; IATA ; OECD
Language	English
Dates of publication	2023-04
Publishing place	Elsevier Ltd
Document type	Article ; Online
ZDB-ID	554791-x
ISSN	1873-6750 ; 0160-4120
ISSN (online)	1873-6750
ISSN	0160-4120
DOI	10.1016/j.envint.2023.107910
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Article ; Online: Assessment of endocrine disruptor impacts on lipid metabolism in a fatty acid-supplemented HepaRG human hepatic cell line.

Bernal, Kévin / Touma, Charbel / Le-Grand, Béatrice / Rose, Sophie / Degerli, Selenay / Genêt, Valentine / Lagadic-Gossmann, Dominique / Coumoul, Xavier / Martin-Chouly, Corinne / Langouët, Sophie / Blanc, Etienne B

Chemosphere

2023 Volume 349, Page(s) 140883

Abstract: The incidence of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing worldwide. This disease encompasses several stages, from steatosis to steatohepatitis and, eventually, to fibrosis and cirrhosis. Exposure to environmental ... ...

Abstract	The incidence of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing worldwide. This disease encompasses several stages, from steatosis to steatohepatitis and, eventually, to fibrosis and cirrhosis. Exposure to environmental contaminants is one of the risk factors and an increasing amount of evidence points to a role for endocrine disrupting compounds (EDCs). This study assesses the impact of selected EDCs on the formation of lipid droplets, the marker for steatosis in a hepatic model. The mechanisms underlying this effect are then explored. Ten compounds were selected according to their obesogenic properties: bisphenol A, F and S, butyl-paraben, cadmium chloride, p,p'-DDE, DBP, DEHP, PFOA and PFOS. Using a 2D or 3D model, HepaRG cells were exposed to the compounds with or without fatty acid supplementation. Then, the formation of lipid droplets was quantified by an automated fluorescence-based method. The expression of genes and proteins involved in lipid metabolism and the impact on cellular respiration was analyzed. The formation of lipid droplets, which is revealed or enhanced by oleic acid supplementation, was most effectively induced by p,p'-DDE and DEHP. Experiments employing either 2D or 3D culture conditions gave similar results. Both compounds induced the expression of PLIN2. p,p'-DDE also appears to act by decreasing in fatty acid oxidation. Some EDCs were able to induce the formation of lipid droplets, in HepaRG cells, an effect which was increased after supplementation of the cells with oleic acid. A full understanding of the mechanisms of these effects will require further investigation. The novel automated detection method described here may also be useful in the future as a regulatory test for EDC risk assessment.
MeSH term(s)	Humans ; Lipid Metabolism ; Fatty Acids/metabolism ; Endocrine Disruptors/metabolism ; Oleic Acid/toxicity ; Oleic Acid/metabolism ; Dichlorodiphenyl Dichloroethylene/metabolism ; Diethylhexyl Phthalate/toxicity ; Fatty Liver/metabolism ; Hepatocytes
Chemical Substances	Fatty Acids ; Endocrine Disruptors ; Oleic Acid (2UMI9U37CP) ; Dichlorodiphenyl Dichloroethylene (4M7FS82U08) ; Diethylhexyl Phthalate (C42K0PH13C)
Language	English
Publishing date	2023-12-11
Publishing country	England
Document type	Journal Article
ZDB-ID	120089-6
ISSN	1879-1298 ; 0045-6535 ; 0366-7111
ISSN (online)	1879-1298
ISSN	0045-6535 ; 0366-7111
DOI	10.1016/j.chemosphere.2023.140883
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Article ; Online: Associations between perfluoroalkyl substances and the severity of non-alcoholic fatty liver disease.

David, Norma / Antignac, Jean-Philippe / Roux, Marine / Marchand, Philippe / Michalak, Sophie / Oberti, Fréderic / Fouchard, Isabelle / Lannes, Adrien / Blanchet, Odile / Cales, Paul / Blanc, Etienne B / Boursier, Jérôme / Canivet, Clémence M

Environment international

2023 Volume 180, Page(s) 108235

Abstract: Background: Non-alcoholic fatty liver disease (NAFLD) has become the leading cause of chronic liver disease worldwide and the determinants driving its severity remain to be elucidated. Perfluoroalkyl substances (PFAS) are synthetic chemical compounds. ... ...

Abstract	Background: Non-alcoholic fatty liver disease (NAFLD) has become the leading cause of chronic liver disease worldwide and the determinants driving its severity remain to be elucidated. Perfluoroalkyl substances (PFAS) are synthetic chemical compounds. They are used in commonplace products and persistent in water, soil and the human body. In vitro and animal studies suggest a pathogenic role for PFAS in metabolic diseases such as NAFLD. Objectives: We aimed to evaluate the association between NAFLD severity and serum PFAS concentrations in humans. Methods: One hundred biopsy-proven NAFLD patients were included with a well-balanced distribution between the different stages of severity: 25 patients with simple steatosis, 25 with early non-alcoholic steatohepatitis (NASH and F0-F1 fibrosis), 33 with fibrotic NASH (NASH and F2-F3 fibrosis), and 17 with cirrhotic NASH (NASH and F4 fibrosis). Liver histological features were evaluated according to the NASH Clinical Research Network classification. Seventeen PFAS were measured by high-performance liquid chromatography coupled with tandem mass spectrometry on serum samples stored at -80 °C. Results: The median age was 60 years, 61 % of patients were male, 46 % had diabetes and the median body mass index (BMI) was 32 kg/m Discussion: Our study showed a significant association between PFHpA and liver steatosis in NAFLD. According to data available in the literature, PFHpA could be implicated in liver steatosis through β-oxidation and biosynthesis of fatty acids.
Language	English
Publishing date	2023-09-27
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	554791-x
ISSN	1873-6750 ; 0160-4120
ISSN (online)	1873-6750
ISSN	0160-4120
DOI	10.1016/j.envint.2023.108235
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Article ; Online: SDHi fungicides: An example of mitotoxic pesticides targeting the succinate dehydrogenase complex.

Duarte Hospital, Carolina / Tête, Arnaud / Debizet, Kloé / Imler, Jules / Tomkiewicz-Raulet, Céline / Blanc, Etienne B / Barouki, Robert / Coumoul, Xavier / Bortoli, Sylvie

Environment international

2023 Volume 180, Page(s) 108219

Abstract: Succinate dehydrogenase inhibitors (SDHi) are fungicides used to control the proliferation of pathogenic fungi in crops. Their mode of action is based on blocking the activity of succinate dehydrogenase (SDH), a universal enzyme expressed by all species ... ...

Abstract	Succinate dehydrogenase inhibitors (SDHi) are fungicides used to control the proliferation of pathogenic fungi in crops. Their mode of action is based on blocking the activity of succinate dehydrogenase (SDH), a universal enzyme expressed by all species harboring mitochondria. The SDH is involved in two interconnected metabolic processes for energy production: the transfer of electrons in the mitochondrial respiratory chain and the oxidation of succinate to fumarate in the Krebs cycle. In humans, inherited SDH deficiencies may cause major pathologies including encephalopathies and cancers. The cellular and molecular mechanisms related to such genetic inactivation have been well described in neuroendocrine tumors, in which it induces an oxidative stress, a pseudohypoxic phenotype, a metabolic, epigenetic and transcriptomic remodeling, and alterations in the migration and invasion capacities of cancer cells, in connection with the accumulation of succinate, an oncometabolite, substrate of the SDH. We will discuss recent studies reporting toxic effects of SDHi in non-target organisms and their implications for risk assessment of pesticides. Recent data show that the SDH structure is highly conserved during evolution and that SDHi can inhibit SDH activity in mitochondria of non-target species, including humans. These observations suggest that SDHi are not specific inhibitors of fungal SDH. We hypothesize that SDHi could have toxic effects in other species, including humans. Moreover, the analysis of regulatory assessment reports shows that most SDHi induce tumors in animals without evidence of genotoxicity. Thus, these substances could have a non-genotoxic mechanism of carcinogenicity that still needs to be fully characterized and that could be related to SDH inhibition. The use of pesticides targeting mitochondrial enzymes encoded by tumor suppressor genes raises questions on the risk assessment framework of mitotoxic pesticides. The issue of SDHi fungicides is therefore a textbook case that highlights the urgent need for changes in regulatory assessment.
MeSH term(s)	Animals ; Humans ; Fungicides, Industrial/toxicity ; Pesticides ; Succinate Dehydrogenase/genetics ; Succinate Dehydrogenase/metabolism ; Fungi/metabolism ; Succinic Acid ; Succinates
Chemical Substances	Fungicides, Industrial ; Pesticides ; Succinate Dehydrogenase (EC 1.3.99.1) ; Succinic Acid (AB6MNQ6J6L) ; Succinates
Language	English
Publishing date	2023-09-19
Publishing country	Netherlands
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	554791-x
ISSN	1873-6750 ; 0160-4120
ISSN (online)	1873-6750
ISSN	0160-4120
DOI	10.1016/j.envint.2023.108219
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Article ; Online: ReadEDTest: A tool to assess the readiness of in vitro test methods under development for identifying endocrine disruptors.

Crouzet, Thibault / Grignard, Elise / Brion, François / Blanc, Etienne B / Podechard, Normand / Langouet, Sophie / Alonso-Magdalena, Paloma / Hubert, Philippe / Kim, Min Ji / Audouze, Karine

Environment international

2023 Volume 174, Page(s) 107910

Abstract	Growing evidence shows that endocrine disruptors (EDs), known to affect the reproductive system, may also disturb other hormone-regulated functions leading to cancers, neurodevelopmental defects, metabolic and immune diseases. To reduce exposure to EDs and limit their health effects, development of screening and mechanism-based assays to identify EDs is encouraged. Nevertheless, the crucial validation step of test methods by regulatory bodies is a time- and resource-consuming process. One of the main raisons of this long duration process is that method developers, mainly researchers, are not fully aware of the regulatory needs to validate a test. We propose an online self-assessment questionnaire (SAQ) called ReadEDTest easy to be used by all researchers. The aim of ReadEDTest is to speed up the validation process by assessing readiness criteria of in vitro and fish embryo ED test methods under development. The SAQ is divided into 7 sections and 13 sub-sections containing essential information requested by the validating bodies. The readiness of the tests can be assessed by specific score limits for each sub-section. Results are displayed via a graphical representation to help identification of the sub-sections having sufficient or insufficient information. The relevance of the proposed innovative tool was supported using two test methods already validated by the OECD and four under development test methods.
MeSH term(s)	Animals ; Endocrine Disruptors/toxicity ; Endocrine Disruptors/metabolism ; In Vitro Techniques
Chemical Substances	Endocrine Disruptors
Language	English
Publishing date	2023-03-31
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	554791-x
ISSN	1873-6750 ; 0160-4120
ISSN (online)	1873-6750
ISSN	0160-4120
DOI	10.1016/j.envint.2023.107910
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Article ; Online: Mitochondrial Dysfunction as a Hallmark of Environmental Injury.

Duarte-Hospital, Carolina / Tête, Arnaud / Brial, François / Benoit, Louise / Koual, Meriem / Tomkiewicz, Céline / Kim, Min Ji / Blanc, Etienne B / Coumoul, Xavier / Bortoli, Sylvie

Cells

2021 Volume 11, Issue 1

Abstract: Environmental factors including diet, sedentary lifestyle and exposure to pollutants largely influence human health throughout life. Cellular and molecular events triggered by an exposure to environmental pollutants are extremely variable and depend on ... ...

Abstract	Environmental factors including diet, sedentary lifestyle and exposure to pollutants largely influence human health throughout life. Cellular and molecular events triggered by an exposure to environmental pollutants are extremely variable and depend on the age, the chronicity and the doses of exposure. Only a fraction of all relevant mechanisms involved in the onset and progression of pathologies in response to toxicants has probably been identified. Mitochondria are central hubs of metabolic and cell signaling responsible for a large variety of biochemical processes, including oxidative stress, metabolite production, energy transduction, hormone synthesis, and apoptosis. Growing evidence highlights mitochondrial dysfunction as a major hallmark of environmental insults. Here, we present mitochondria as crucial organelles for healthy metabolic homeostasis and whose dysfunction induces critical adverse effects. Then, we review the multiple mechanisms of action of pollutants causing mitochondrial toxicity in link with chronic diseases. We propose the Aryl hydrocarbon Receptor (AhR) as a model of "exposome receptor", whose activation by environmental pollutants leads to various toxic events through mitochondrial dysfunction. Finally, we provide some remarks related to mitotoxicity and risk assessment.
MeSH term(s)	Apoptosis ; Environmental Pollutants/adverse effects ; Humans ; Mitochondria/pathology ; Xenobiotics/pharmacology ; Xenobiotics/therapeutic use
Chemical Substances	Environmental Pollutants ; Xenobiotics
Language	English
Publishing date	2021-12-30
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells11010110
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Article ; Online: New approach methodologies to enhance human health risk assessment of immunotoxic properties of chemicals - a PARC (Partnership for the Assessment of Risk from Chemicals) project.

Snapkow, Igor / Smith, Nicola M / Arnesdotter, Emma / Beekmann, Karsten / Blanc, Etienne B / Braeuning, Albert / Corsini, Emanuela / Sollner Dolenc, Marija / Duivenvoorde, Loes P M / Sundstøl Eriksen, Gunnar / Franko, Nina / Galbiati, Valentina / Gostner, Johanna M / Grova, Nathalie / Gutleb, Arno C / Hargitai, Rita / Janssen, Aafke W F / Krapf, Solveig A / Lindeman, Birgitte /

Lumniczky, Katalin / Maddalon, Ambra / Mollerup, Steen / Parráková, Lucia / Pierzchalski, Arkadiusz / Pieters, Raymond H H / Silva, Maria J / Solhaug, Anita / Staal, Yvonne C M / Straumfors, Anne / Szatmári, Tünde / Turner, Jonathan D / Vandebriel, Rob J / Zenclussen, Ana Claudia / Barouki, Robert

Frontiers in toxicology

2024 Volume 6, Page(s) 1339104

Abstract: As a complex system governing and interconnecting numerous functions within the human body, the immune system is unsurprisingly susceptible to the impact of toxic chemicals. Toxicants can influence the immune system through a multitude of mechanisms, ... ...

Abstract	As a complex system governing and interconnecting numerous functions within the human body, the immune system is unsurprisingly susceptible to the impact of toxic chemicals. Toxicants can influence the immune system through a multitude of mechanisms, resulting in immunosuppression, hypersensitivity, increased risk of autoimmune diseases and cancer development. At present, the regulatory assessment of the immunotoxicity of chemicals relies heavily on rodent models and a limited number of Organisation for Economic Co-operation and Development (OECD) test guidelines, which only capture a fraction of potential toxic properties. Due to this limitation, various authorities, including the World Health Organization and the European Food Safety Authority have highlighted the need for the development of novel approaches without the use of animals for immunotoxicity testing of chemicals. In this paper, we present a concise overview of ongoing efforts dedicated to developing and standardizing methodologies for a comprehensive characterization of the immunotoxic effects of chemicals, which are performed under the EU-funded Partnership for the Assessment of Risk from Chemicals (PARC).
Language	English
Publishing date	2024-04-09
Publishing country	Switzerland
Document type	Journal Article ; Review
ISSN	2673-3080
ISSN (online)	2673-3080
DOI	10.3389/ftox.2024.1339104
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Article: A dual mixture of persistent organic pollutants modifies carbohydrate metabolism in the human hepatic cell line HepaRG

Leblanc, Alix F / Aggerbeck, Martine / Attignon, Eléonore A / Barouki, Robert / Blanc, Etienne B / Bortoli, Sylvie / Coumoul, Xavier / Distel, Emilie / Karakitsios, Spyros P / Sarigiannis, Dimosthenis A

Environmental research. 2019 Aug. 04,

2019

Abstract: Individuals as well as entire ecosystems are exposed to mixtures of Persistent Organic Pollutants (POPs). Previously, we showed, by a non-targeted approach, that the expression of several genes involved in carbohydrate metabolism was almost completely ... ...

Abstract	Individuals as well as entire ecosystems are exposed to mixtures of Persistent Organic Pollutants (POPs). Previously, we showed, by a non-targeted approach, that the expression of several genes involved in carbohydrate metabolism was almost completely inhibited in the human hepatic cell line HepaRG following exposure to a mixture of the organochlorine insecticide alpha-endosulfan and 2,3,7,8 tetrachlorodibenzo-p-dioxin. In this European HEALS project, which studies the effects of the exposome on human health, we used a Physiologically Based BioKinetic model to compare the concentrations previously used in vitro with in vivo exposures for humans. We investigated the effects of these POPs on the levels of proteins, on glycogen content, glucose production and the oxidation of glucose into CO2 and correlated them to the expression of genes involved in carbohydrate metabolism as measured by RT-qPCR. Exposure to individual POPs and the mixture decreased the expression of the proteins investigated as well as glucose output (up to 82%), glucose oxidation (up to 29%) and glycogen content (up to 48%). siRNAs that specifically inhibit the expression of several xenobiotic receptors were used to assess receptor involvement in the effects of the POPs. In the HepaRG model, we demonstrate that the effects are mediated by the Aryl Hydrocarbon Receptor and the estrogen receptor alpha, but not the pregnane X receptor or the constitutive androstane receptor. These results provide evidence that exposure to combinations of POPs, acting through different signaling pathways, may affect, more profoundly than single pollutants alone, metabolic pathways such as carbohydrate/energy metabolism and play a potential role in pollutant associated metabolic disorders.
Keywords	alpha-endosulfan ; androstanes ; aromatic compounds ; biochemical pathways ; carbohydrate metabolism ; carbon dioxide ; ecosystems ; energy metabolism ; estrogen receptors ; gene expression ; genes ; glucose ; glycogen ; human cell lines ; human health ; humans ; metabolic diseases ; models ; oxidation ; persistent organic pollutants ; pregnanes ; quantitative polymerase chain reaction ; reverse transcriptase polymerase chain reaction ; signal transduction ; small interfering RNA ; tetrachlorodibenzo-p-dioxin ; xenobiotics
Language	English
Dates of publication	2019-0804
Publishing place	Elsevier Inc.
Document type	Article
Note	Pre-press version
ZDB-ID	205699-9
ISSN	1096-0953 ; 0013-9351
ISSN (online)	1096-0953
ISSN	0013-9351
DOI	10.1016/j.envres.2019.108628
Database	NAL-Catalogue (AGRICOLA)

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