Éditeur(s) : HAL CCSD
Résumé : International audience
BACKGROUND: The aryl hydrocarbon receptor (AhR) has gradually emerged as a regulator of inflammation in the lung and other tissues. AhR may interact with the p65-subunit of the nuclear factor (NF)-κB transcription factors, but reported outcomes of AhR/NF-κB-interactions are conflicting. Some studies suggest that AhR possess pro-inflammatory activities while others suggest that AhR may be anti-inflammatory. The present study explored the impact of AhR and its binding partner AhR nuclear translocator (Arnt) on p65-activation and two differentially regulated chemokines, CXCL8 (IL-8) and CCL5 (RANTES), in human bronchial epithelial cells (BEAS-2B). RESULTS: Cells were exposed to CXCL8- and CCL5-inducing chemicals, 1-nitropyrene (1-NP) and 1-aminopyrene (1-AP) respectively, or the synthetic double-stranded RNA analogue, polyinosinic-polycytidylic acid (Poly I:C) which induced both chemokines. Only CXCL8, and not CCL5, appeared to be p65-dependent. Yet, constitutively active unligated AhR suppressed both CXCL8 and CCL5, as shown by siRNA knock-down and the AhR antagonist α-naphthoflavone. Moreover, AhR suppressed activation of p65 by TNF-α and Poly I:C as assessed by luciferase-assay and p65-phosphorylation at serine 536, without affecting basal p65-activity. In contrast, Arnt suppressed only CXCL8, but did not prevent the p65-activation directly. However, Arnt suppressed expression of the NF-κB-subunit RelB which is under transcriptional regulation by p65. Furthermore, AhR-ligands alone at high concentrations induced a moderate CXCL8-response, without affecting CCL5, but suppressed both CXCL8 and CCL5-responses by Poly I:C. CONCLUSION: AhR and Arnt may differentially and independently regulate chemokine-responses induced by both inhaled pollutants and pulmonary infections. Constitutively active, unligated AhR suppressed the activation of p65, while Arnt may possibly interfere with the action of activated p65. Moreover, ligand-activated AhR suppressed CXCL8 and CCL5 responses by other agents, but AhR ligands alone induced CXCL8 responses when given at sufficiently high concentrations, thus underscoring the duality of AhR in regulation of inflammation. We propose that AhR-signaling may be a weak activator of p65-signaling that suppresses p65-activity induced by strong activators of NF-κB, but that its anti-inflammatory properties also are due to interference with additional pathways.
Cell communication and signaling: CCS

hal-01063555
https://hal.archives-ouvertes.fr/hal-01063555
DOI : 10.1186/s12964-014-0048-8

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Endocrine disrupting chemicals and especially oestrogen receptor (ER) agonists have been extensively studied over the years due to their potential effects on sexual development and reproduction in vertebrates, notably fish. As ER agonists can exist as complex mixtures in the aquatic environment, evaluating the impact of combined exposure on oestrogenic effects has become increasingly important. Use of predictive models such as concentration addition (CA) and independent action (IA) has allowed assessment of combined estrogenic effects of complex multi-compound mixtures of ER agonists in various fish in vitro and in vivo experimental models. The present work makes use of a transgenic zebrafish strain, tg(cyp19a1b-GFP), which expresses the green fluorescent protein (GFP) under the control of the cyp19a1b (brain aromatase or aromatase B) gene to determine the oestrogenic potency of ER agonists alone or in mixtures. In these studies, tg(cyp19a1b-GFP) zebrafish embryos were exposed for four days (from one to five days post fertilization) to five different oestrogenic chemicals; 17α-ethinylestradiol (EE2), 17β-estradiol (E2), estrone (E1), bisphenol A (BPA) and 4-tert-octylphenol (OP), and three mixtures of up to four of these compounds. The mixture of BPA, OP and E2 was also tested with primary cultures of rainbow trout hepatocytes by analysing the ER-mediated induction of the oestrogenic biomarker vitellogenin in order to compare the performance of the two methods for assessing oestrogenic effects of complex mixtures. The three tested mixtures were predominantly acting in an additive manner on the expression of GFP. Additivity was indicated by the overlap of the 95% confidence interval of the concentration response curves for the observed data with the CA and IA prediction models, and model deviation ratios within a factor of two for a majority of the mixture concentrations. However, minor deviations determined as more than additive effects for the mixture of EE2, E1 and E2 and less than additive effects for the mixture of BPA, OP, EE2 and E1 were observed at the higher mixture concentrations tested. The successful prediction of additivity by CA and IA in tg(cyp19a1b-GFP) zebrafish embryos and deviations at high mixture concentrations seemed to correspond well to results obtained in the rainbow trout hepatocyte assay. The present results clearly show the usefulness of combining predictive modelling and use of in vitro bioassays for rapid screening of oestrogenic effects of complex mixtures and environmental samples.
ISSN: 0166-445X

hal-00877351
https://hal.archives-ouvertes.fr/hal-00877351
DOI : 10.1016/j.aquatox.2013.05.001
PUBMED : 23721851

Éditeur(s) : The Royal Society
Résumé : One of the most ubiquitous and long-lasting recent changes to the surface of our planet is the accumulation and fragmentation of plastics. Within just a few decades since mass production of plastic products commenced in the 1950s, plastic debris has accumulated in terrestrial environments, in the open ocean, on shorelines of even the most remote islands and in the deep sea. Annual clean-up operations, costing millions of pounds sterling, are now organized in many countries and on every continent. Here we document global plastics production and the accumulation of plastic waste. While plastics typically constitute approximately 10 per cent of discarded waste, they represent a much greater proportion of the debris accumulating on shorelines. Mega- and macro-plastics have accumulated in the highest densities in the Northern Hemisphere, adjacent to urban centres, in enclosed seas and at water convergences ( fronts). We report lower densities on remote island shores, on the continental shelf seabed and the lowest densities (but still a documented presence) in the deep sea and Southern Ocean. The longevity of plastic is estimated to be hundreds to thousands of years, but is likely to be far longer in deep sea and non-surface polar environments. Plastic debris poses considerable threat by choking and starving wildlife, distributing non-native and potentially harmful organisms, absorbing toxic chemicals and degrading to micro-plastics that may subsequently be ingested. Well-established annual surveys on coasts and at sea have shown that trends in mega- and macro-plastic accumulation rates are no longer uniformly increasing: rather stable, increasing and decreasing trends have all been reported. The average size of plastic particles in the environment seems to be decreasing, and the abundance and global distribution of micro-plastic fragments have increased over the last few decades. However, the environmental consequences of such microscopic debris are still poorly understood.
Philosophical Transactions of the Royal Society B (0962-8436) (The Royal Society), 2009-07 , Vol. 364 , N. 1526 , P. 1985-1998

Droits : The Royal Society 2009
http://archimer.ifremer.fr/doc/2009/publication-6952.pdf
DOI:10.1098/rstb.2008.0205
http://archimer.ifremer.fr/doc/00000/6952/

Éditeur(s) : HAL CCSD
Résumé : International audience
Estrogens and progestins are widely used in combination in human medicine and both are present in aquatic environment. Despite the joint exposure of aquatic wildlife to estrogens and progestins, very little information is available on their combined effects. In the present study we investigated the effect of ethinylestradiol (EE2) and Levonorgestrel (LNG), alone and in mixtures, on the expression of the brain specific ER-regulated cyp19a1b gene. For that purpose, recently established zebrafish-derived tools were used: (i) an in vitro transient reporter gene assay in a human glial cell line (U251-MG) co-transfected with zebrafish estrogen receptors (zfERs) and the luciferase gene under the control of the zebrafish cyp19a1b gene promoter and (ii) an in vivo bioassay using a transgenic zebrafish expressing GFP under the control of the zebrafish cyp19a1b gene promoter (cyp19a1b-GFP). Concentration-response relationships for single chemicals were modeled and used to design the mixture experiments following a ray design. The results from mixture experiments were analyzed to predict joint effects according to concentration addition and statistical approaches were used to characterize the potential interactions between the components of the mixtures (synergism/antagonism). We confirmed that some progestins could elicit estrogenic effects in fish brain. In mixtures, EE2 and LNG exerted additive estrogenic effects both in vitro and in vivo, suggesting that some environmental progestin could exert effects that will add to those of environmental (xeno-)estrogens. Moreover, our zebrafish specific assays are valuable tools that could be used in risk assessment for both single chemicals and their mixtures. © 2016 Elsevier Inc.
Toxicology and Applied Pharmacology

hal-01367151
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01367151
DOI : 10.1016/j.taap.2016.07.023
PUBMED : 27491593

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Mixtures of polybrominated diphenyl ethers (PBDEs) are present in indoor environments. Studies of the developmental effects of exposure to these chemicals in large prospective mother-child cohorts are required, with data on prenatal exposure and long-term follow-up of the children. We aimed to investigate the relationship between prenatal and childhood exposure to PBDEs and neurodevelopment at the age of six years. We determined the levels of PBDEs and other neurotoxicants in cord blood and dust collected from the homes of children for 246 families included in the PELAGIE mother-child cohort in France. We assessed two cognitive domains of the six-year-old children using the Wechsler Intelligence Scale for Children-IV. Verbal comprehension scores were lower in children from homes with higher concentrations of BDE99 (βDetects < median_vs_NonDetects = −1.6; 95% CI: −6.1, 2.9; βDetects≥median_vs_NonDetects = −5.4; −9.9, −1.0; ptrend = 0.02) and of BDE209 (β2nd_vs₁st_tertile = −1.8; 95% CI: −6.1, 2.5; β3rd_vs₁st_tertile = −3.2; −7.5, 1.2; ptrend = 0.15) in dust, particularly for boys (ptrend = 0.02 and 0.04, respectively). Working memory scores seemed to be lower in children with higher BDE99 concentrations in dust (ptrend = 0.10). No association was observed with cord blood levels of BDE209. Our findings are in agreement with those of four previous studies suggesting adverse cognitive outcomes among children associated with early-life exposure to penta-BDE mixtures, and provide new evidence for the potential neurotoxicity of BDE209. Several countries are in the process of banning the use of PBDE mixtures as flame-retardants. However, these compounds are likely to remain present in the environment for a long time to come
ISSN: 0161-813X

hal-01286255
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01286255
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01286255/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01286255/file/Childhood%20exposure%20to%20polybrominated%20diphenyl-accepted.pdf
DOI : 10.1016/j.neuro.2016.03.002

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
Diesel exhaust particles (DEPs) are common environmental air pollutants primarily affecting the lung. DEPs or chemicals adsorbed on DEPs also exert extra-pulmonary effects, including alteration of hepatic drug detoxifying enzyme expression. The present study was designed to determine whether organic DEP extract (DEPe) may target hepatic drug transporters that contribute in a major way to drug detoxification. Using primary human hepatocytes and transporter-overexpressing cells, DEPe was first shown to strongly inhibit activities of the sinusoidal solute carrier (SLC) uptake transporters organic anion-transporting polypeptides (OATP) 1B1, 1B3 and 2B1 and of the canalicular ATP-binding cassette (ABC) efflux pump multidrug resistance-associated protein 2, with IC50 values ranging from approximately 1 to 20 μg/mL and relevant to environmental exposure situations. By contrast, 25 μg/mL DEPe failed to alter activities of the SLC transporter organic cation transporter (OCT) 1 and of the ABC efflux pumps P-glycoprotein and bile salt export pump (BSEP), whereas it only moderately inhibited those of sodium taurocholate co-transporting polypeptide and of breast cancer resistance protein (BCRP). Treatment by 25 μg/mL DEPe was next demonstrated to induce expression of BCRP at both mRNA and protein level in cultured human hepatic cells, whereas it concomitantly repressed mRNA expression of various transporters, including OATP1B3, OATP2B1, OCT1 and BSEP. Such changes in transporter expression were found to be highly correlated to those caused by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a reference activator of the aryl hydrocarbon receptor (AhR) pathway. This suggests that DEPe, which is enriched in known ligands of AhR like polycyclic aromatic hydrocarbons, alters drug transporter expression via activation of the AhR cascade. Taken together, these data established human hepatic transporters as targets of organic chemicals containing in DEPs, which may contribute to their systemic effects through impairing hepatic transport of endogenous compound or drug substrates of these transporters.
ISSN: 1932-6203

Droits : http://creativecommons.org/licenses/by/
hal-01138535
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01138535
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01138535/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01138535/file/Regulation%20of%20human%20hepatic%20drug.pdf
DOI : 10.1371/journal.pone.0121232

Éditeur(s) : HAL CCSD
Résumé : International audience
BACKGROUND: Africa faces a number of unique environmental challenges. Unfortunately, it lacks the infrastructure needed to support the comprehensive environmental studies that could provide the scientific basis to inform environmental policies. There are a number of known sources of endocrine-disrupting chemicals (EDCs) and other hazardous chemicals in Africa. However, a coordinated approach to identify and monitor these contaminants and to develop strategies for public health interventions has not yet been made. OBJECTIVES: This commentary summarizes the scientific evidence presented by experts at the First African Endocrine Disruptors meeting. We describe a "call to action" to utilize the available scientific knowledge to address the impact of EDCs on human and wildlife health in Africa. DISCUSSION: We identify existing knowledge gaps about exposures to EDCs in Africa and describe how well-designed research strategies are needed to address these gaps. A lack of resources for research and a lag in policy implementation slows down intervention strategies and poses a challenge to advancing future health in Africa. CONCLUSION: To address the many challenges posed by EDCs, we argue that Africans should take the lead in prioritization and evaluation of environmental hazards, including EDCs. We recommend the institution of education and training programs for chemical users, adoption of the precautionary principle, establishment of biomonitoring programs, and funding of community-based epidemiology and wildlife research programs led and funded by African institutes and private companies. https://doi.org/10.1289/EHP1774.
Environmental Health Perspectives

hal-01616487
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01616487
DOI : 10.1289/EHP1774
PUBMED : 28935616

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Because earthworms sustain soil functioning and fertility, there is a need to advance the knowledge of their adaptation potential to chemicals in anthropogenic landscapes. Our hypothesis is that there is acclimation to organic chemicals (pesticides) in earthworms that durably persist under conventional farming in anthropogenic landscapes. The adaptation capability of two populations of earthworms (Aporectodea caliginosa) having a different chemical exposure history, - one originating from 20 years of organic farming (naïve population) and another from 20 years of conventional farming (pre-exposed population) - to cope with soil organic pollutant (Opus®, epoxiconazole a worldwide used fungicide) were investigated. Several complementary metabolic and energetic endpoints were followed, and cast production was assessed as a behavioural biomarker related to earthworms ecological role for the soil. Basal metabolism reflected by respiration rate was increased in both fungicide-exposed worms compared to controls. Glycogen resources were decreased in the same proportion in the two populations but more rapidly for the naïve (7 days) than for the pre-exposed population (28 days). Soluble protein and most amino-acids contents increased in the pre-exposed population only, suggesting a detoxification mechanism. Metabolomic profiles showed a cut-off between fungicide-exposed and control groups in the pre-exposed earthworms only, with an increase in most of the metabolites. Exposure to a low dose of epoxiconazole increased cast production of pre-exposed earthworms, and this resulted in an increase in pesticide disappearance. As far as we know, this is the first study which evidenced there is an acclimation to an agricultural chemical in earthworms derived from conventional farming that also relates to a change in their burrowing behaviour, and for which larger consequences for the soil ecosystem need to be addressed. This original finding is of major interest in the frame of ecosystem resilience to global changes. Whether this physiological adaptation is a general pattern of response against fungicides or other pesticides would need to be confirmed with other molecules and agricultural contexts.
Soil Biology and Biochemistry

hal-01005821
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01005821
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01005821/document
DOI : 10.1016/j.soilbio.2014.01.032

Résumé : This study contributes to inventory programme on emerging pollutants in French waters and to the general reflection which will enable to update the list of relevant substnaces to be included in the new monitoring programmes to come. This work concerns the coastal part of the inventory programme on marine waters and sediments of France and five overseas french departments (OFD). In this goal, passive sampling techniques and direct extraction techniques have been tested through the implementation of in situ systems integrators POCIS (Polar Organic Chemical Integrative Sampler) and the extraction by SBSE bars (Stir bar sorptive extraction) directly in the waters sampled. Finally, analyzes of sediment completed the acquisition of data. Arount 40 stations were sampled for shore waters and sediments were collected from 7 stations in France and 5 stations in the OFD (one station/OFD). In analytical terms, 1054 analyzes were carried out on POCIS membranes and only 64 data exceeded the limit of detection (LD), 12726 analyzes came from SBSE extractions and 304 were above the LD and 1536 analyzes in sediment showed that 237 data were above the limit of quantification (LQ). Finally, 169 different substances were investigated and 68 of them were detected at least once in water or sediment. The lack of replicates for POCIS analyzes and those in the sediment limited the statistical treatment of data. The results were used to determine the level of contamination, the detection frequency (FD), the distribution of substances between France and OFD, the comparison with environmental thresholds (the PNEC) and the origin/use of the substances. In littoral waters, 32 substances were identified and 19 were quantified. In the sediment, 47 substances were quantified. Nine substances were detected in both water and sediment. In France, the 15 substances that were quantified at higher frequencies (> 50 %, one out of 2 sites) were quantified in sediments. These are the congeners of PAHs (11 substances), organic forms of tin (2 substances), diethyl lead and 209 PBDE congener. In the OFD, the 22 substances that were quantified at higher frequencies (> 50 %, one out of 2 sites) were measured in sediments. These are congeners of PAHs (13 substances) , alkylphenols ( 3 molecules: the mono and diethoxyate nonylphenol and the 4-ter butylphenol ), the organic forms of tin (2 substances), products of metabolism insecticide DDT ( 2 products), diethyl lead and the 209 PBDE congener. The study of the highest concentrations distribution of substances between France and OFD shows that the 5 (among 19 molecules) highest concentrations in water and the 6 (among 47 molecules) highest concentrations in sediments are found in OFD. Reference to PNEC indicates that four pesticides in water and 11 different substances in sediments exceed the environmental thresholds. Substances with highest detection frequency are found in the sediment. The distribution of data by use or nature of the substance shows that plasticizers and pesticides predominate in raw water, both in France and overseas departments while PAHs in sediments dominate in France and in OFD.
Cette étude contribue au programme d’inventaire des substances chimiques émergentes dans les eaux françaises et à la réflexion qui doit permettre d’actualiser la liste des substances pertinentes à surveiller de manière régulière dans le cadre des nouveaux programmes de surveillance. Ce travail concerne la partie littorale de l’inventaire, sur les eaux brutes et les sédiments de la métropole et des 5 DOM. Dans ce cadre, des techniques d’échantillonnage passif (EP) et d’extraction directe ont été testées grâce à la mise en place in situ de systèmes intégrateurs POCIS (Polar Organic Chemical Integrative Sampler) et à l’extraction par des barres SBSE (Stir Bar Sorptive Extraction) directement dans les eaux échantillonnées. Enfin des analyses de sédiments ont complété l’acquisition des données. L’eau d’une quarantaine de stations a été échantillonnée et des sédiments ont été prélevés sur 7 stations en métropole et dans 5 stations dans les DOM (une station par DOM). En termes analytiques, 1054 analyses ont été réalisées sur les membranes POCIS et 64 dépassaient la limite de détection (LD), 12726 analyses ont concerné les extractions par SBSE pour 304 résultats situés au dessus de la LD et 1536 analyses effectuées dans le sédiment ont donné 237 valeurs supérieures à la limite de quantification (LQ). Au bilan 169 substances différentes ont été recherchées et 68 d’entre elles ont été détectées au moins une fois dans l’eau brute ou le sédiment. L’absence de réplicats pour les analyses POCIS et celles dans le sédiment a limité le traitement statistique des données. Les résultats ont permis de déterminer le niveau de contamination, la fréquence de détection (FD), la distribution métropole/DOM des substances, la comparaison avec les seuils environnementaux (PNEC) et l’origine des substances. Dans l’eau 32 substances ont été identifiées et 19 ont été quantifiées. Dans le sédiment 47 substances sont quantifiées .Neuf substances sont détectées à la fois dans l’eau et le sédiment. En métropole, les 15 substances quantifiées aux plus hautes fréquences (> 50%, soit un site sur 2) sont quantifiées dans les sédiments. Ce sont les congénères de la famille des HAP (11 substances), des formes organiques de l’étain (2 substances), le plomb diéthyle et le congénère 209 des PBDE. Dans les DOM, les 22 substances quantifiées aux plus hautes fréquences (> 50%, soit un site sur 2) sont mesurées dans les sédiments. Ce sont des congénères de la famille des HAP dans (13 substances), des alkylphénols (3 substances : nonylphénols mono et diéthoxylés et 4-ter butylphénol), des formes organiques de l’étain (2 substances), des produits de métabolisation de l’insecticide DDT (2 produits), du plomb diéthyle et du congénère 209 des PBDE. L’étude de la répartition des plus fortes concentrations entre la métropole et les DOM montre que les 5 (sur 19) concentrations les plus élevées mesurées dans l’eau et les 6 (sur 47) plus fortes concentrations mesurées dans les sédiments sont trouvées dans les DOM. Les substances mesurées aux fortes fréquences sont observées dans le sédiment. La référence à la PNEC indique le dépassement de la norme pour 4 pesticides dans l’eau brute et 11 substances diverses dans les sédiments. L’exploitation des données par usage ou nature des substances montre que les plastifiants et les pesticides sont majoritaires dans les eaux brutes, à la fois en métropole et dans les DOM alors que ce sont les HAP qui dominent dans les sédiments, en métropole et dans les DOM.

Droits : 2014 ONEMA, Ifremer
http://archimer.ifremer.fr/doc/00259/36994/35483.pdf
http://archimer.ifremer.fr/doc/00259/36994/

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
Exposure to solvents during pregnancy has long been suspected to increase the risk of congenital malformations. Glutathione S-transferases (GSTs) are enzymes essential for the detoxification of various chemicals. Our objective here was to assess whether GST polymorphisms might modify the association between maternal solvent exposure and the risk of birth defects. A prospective cohort included 3421 pregnant women in Brittany, France (2002-2006). Occupational exposure to solvents was assessed from a job-exposure matrix. Congenital malformations were diagnosed among livebirths, stillbirths, and medical pregnancy terminations. Using a nested case-control design, 32 babies with major birth defects were compared to 348 normal births for babies' cord blood genotypes (at GSTT1 and GSTM1) and maternal occupational solvent exposure. Logistic models were used to adjust for potential confounders. The risk of major defects increased significantly in women with solvent exposure (20% of controls and 34% of cases). Frequencies of the null genotype of both the GSTT1 and GSTM1 genes were similar among controls and cases. There was a significantly increased risk of birth defects in GSTM1 not-null cord-blood genotype in pregnancies exposed to solvents (odds ratio [OR], 1.0 for not-null, not-exposed; OR, 4.0 for not-null, exposed; 95% confidence interval [CI], 1.4-11.2; OR, 1.6 for null, not-exposed; 95% CI, 0.6-3.9; OR, 1.0 for null, exposed; 95% CI, 0.2-4.7; p = 0.05). This nested case-control study suggests that the child's GSTM1 genotype modifies the risk of major birth defects among offspring of solvent-exposed women. Replication and additional investigations are necessary to confirm and elucidate these findings.
ISSN: 1542-0752

hal-00875957
https://hal.archives-ouvertes.fr/hal-00875957
DOI : 10.1002/bdra.23018
PUBMED : 22570144

Éditeur(s) : Actes de colloques. Ifremer. Brest [ACTES COLLOQ. IFREMER.]. 1986
Résumé : Five topics are developed in this synthesis: (1) multi elements analysis in geochemistry; (2) iron geochemical behavior; (3) complexing properties of waters; (4) copper behavior in estuarine waters; (5) impact of sediment dynamics on dissolved metals concentration.

Droits : info:eu-repo/semantics/openAccess
http://archimer.ifremer.fr/doc/1985/acte-1290.pdf
http://archimer.ifremer.fr/doc/00000/1290/

Éditeur(s) : HAL CCSD MDPI
Résumé : International audience
The number and amount of man-made chemicals present in the aquatic environment has increased considerably over the past 50 years. Among these contaminants, endocrine-disrupting chemicals (EDCs) represent a significant proportion. This family of compounds interferes with normal hormonal processes through multiple molecular pathways. They represent a potential risk for human and wildlife as they are suspected to be involved in the development of diseases including, but not limited to, reprotoxicity, metabolic disorders, and cancers. More precisely, several studies have suggested that the increase of breast cancers in industrialized countries is linked to exposure to EDCs, particularly estrogen-like compounds. Estrogen receptors alpha (ERα) and beta (ERβ) are the two main transducers of estrogen action and therefore important targets for these estrogen-like endocrine disrupters. More than 70% of human breast cancers are ERα-positive and estrogen-dependent, and their development and growth are not only influenced by endogenous estrogens but also likely by environmental estrogen-like endocrine disrupters. It is, therefore, of major importance to characterize the potential estrogenic activity from contaminated surface water and identify the molecules responsible for the hormonal effects. This information will help us understand how environmental contaminants can potentially impact the development of breast cancer and allow us to fix a maximal limit to the concentration of estrogen-like compounds that should be found in the environment. The aim of this review is to provide an overview of emerging estrogen-like compounds in the environment, sum up studies demonstrating their direct or indirect interactions with ERs, and link their presence to the development of breast cancer. Finally, we emphasize the use of in vitro and in vivo methods based on the zebrafish model to identify and characterize environmental estrogens.
ISSN: 2073-4425

hal-01616486
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01616486
DOI : 10.3390/genes8090229
PUBMED : 28914763
PUBMEDCENTRAL : PMC5615362

Résumé : La banane plantain (Musa paradisiaca) est l’aliment de base de millions de personnes dans le monde et sa culture génère des revenus permanents pour un grand nombre d’agriculteurs, dans des plantations de taille petite ou moyenne. Comme dans d’autres régions tropicales, la culture du plantain en Guadeloupe et en Haïti est soumise à de fortes contraintes parasitaires aussi bien telluriques (i.e. du sol : nématodes phytoparasites et charançon du bananier) qu’aériennes (Cercosporiose noire notamment). Les moyens de lutte conventionnels reposent sur l’usage de produits de synthèse dont les effets néfastes sur l’environnement (sols, eaux, animaux) comme sur la santé humaine ne sont plus supportables. Il est donc urgent de réfléchir à des solutions agro-écologiques permettant de rétablir les équilibres biologiques, de maintenir une bonne qualité des sols et une production optimale dans les systèmes de culture plantains. C’est le but de ce travail de thèse qui couple la réalisation d’un diagnostic agro-écologique dans des parcelles paysannes, et le test d’alternatives agro-écologiques en milieu semi-contrôlé. Pour ce faire, une typologie des systèmes de culture plantains a été réalisée à l’issue d’une enquête agro-environnementale dans les deux zones d’étude. Elle a permis de sélectionner 23 parcelles en Guadeloupe et 12 en Haïti dans lesquelles un diagnostic agro-écologique a été conduit. Sur la base de ce diagnostic et de la recherche d’alternatives agro-écologiques à l’usage des produits chimiques, une expérimentation au champ a été mise en place en Guadeloupe en station de recherche, permettant le test de trois pratiques culturales innovantes pour le plantain (seules et combinées), à savoir : i) l’introduction d’une plante de service Paspalum notatum pour la gestion des adventices et la réduction de l’utilisation d’herbicides ; ii) l’apport de vermicompost pour le contrôle des nématodes phytoparasites inféodés au bananier plantain et la fertilisation de celui-ci ; iii) l’utilisation de plants sains PIF (Plants Issus de Fragments de tiges) indemnes de nématodes et de larves de charançon du bananier. La typologie des systèmes de culture plantains révèle que : i) en Guadeloupe les précédents : jachère, ananas et banane plantain sont prédominants avec un niveau d’intensification faible (apports d’intrants chimiques faibles et peu fréquents) ou élevé (apports d’intrants chimiques élevés et plus fréquents) ; ii) en Haïti, les précédents : jachère, banane plantain et manioc prédominent avec un niveau d’intensification faible ou nul (apport d’intrants inexistant). Les résultats du diagnostic agro-écologique montrent que, i) lorsque le niveau d’intensification est faible, les bananeraies plantains pérennes et le précédent-ananas permettent de maintenir une bonne qualité du sol et une bonne régulation des parasites telluriques ; ii) lorsque le niveau d’intensification est fort, les populations d’ingénieurs du sol diminuent drastiquement, alors que le cortège parasitaire tellurique augmente sans que cela n’affecte l’obtention de bons niveaux de rendement instantannés (parcelles précédées d’ananas ou d’une jachère principalement) ; iii) en absence totale de fertilisation, il résulte une diminution de l’activité biologique du sol mais aussi du rendement du plantain, exacerbé par le choix des précédents-culturaux (manioc ou banane plantain) en lien avec les contraintes pédoclimatiques et la maladie des raies noires (Cercosporiose noire) causée par Mycosphaerella fijiensis, notamment au sein des parcelles Haïtiennes ; iv) la succession plantain/plantain est la plus pénalisante vis-à-vis de la culture du plantain, car quelque soit le niveau d’intensification, le rendement reste relativement faible, en lien avec une dégradation de l’état sanitaire, comparativement aux autres précédents.
Plantain (Musa paradisiaca) is the staple food of millions of people worldwide and its cropping generates ongoing revenues for many farmers who are planting small or medium size areas. As in other tropical regions, plantain cultivation in Guadeloupe and Haiti is under heavy parasitic constraints terrestrial (plant-parasitic nematodes and banana weevil) as well as aerial (black Sigatoka in particular). Conventional means of control based on the use of synthetic products which adverse effects on the environment (soil, water, animals ...) as on human health are not bearable any more. It is thus urgent to think about agroecological solutions allowing to restore the biological balances, to maintain good soil quality and optimal plantain cropping systems.This is the ultimate goal of this thesis which couples the realization of an agroecological diagnosis in peasants’ plots, and the test of agroecological alternatives in semi-controlled conditions. To do this, a typology of plantain cropping systems was carried out from an agrienvironmental survey in the two study areas. It allowed to select 23 plots in Guadeloupe and 12 in Haiti in which an agroecological diagnosis was implemented. Based on this diagnosis and the research of agroecological alternatives to the use of chemicals, a field experiment was set up in Guadeloupe, in an experimental station allowing the test of three innovative practices for plantain cultivation (alone and combined), namely : i) the introduction of a cover-crop Paspalum notatum for weed control while reducing the use of herbicides ; ii) the input of worms’ compost to control plant-parasitic nematodes specific to plantain and to fertilize it ; iii) the use of healthy “PIF” plants (plants issued from stem fragments) free from telluric pests (nematodes and weevil’s larvaes).The typology of plantains cropping systems shows: i) in Guadeloupe the previous crops are: fallow pineapple and plantain predominate with a low level of intensification (low and infrequent chemical inputs) or high (high and frequent chemical inputs); ii) in Haiti, the previous crops are: fallow, plantain and cassava predominate with a low level or no intensification at all (no inputs). The results of the agroecological analysis show that : i) when the level of intensification is low, perennial plantain and pineapple as previous crops help maintaining a good soil quality and a good regulation of the telluric pests ; ii) when the level of intensification is strong, the soil engineers drastically reduce, while the density of telluric parasites increases without affecting good levels of instantaneous yields (plots where the previous crop is pineapple or mostly fallow) ; iii) when the fertilization is totally missing, it decreases the biological activity of the soil furthermore the plantain yields, exacerbated by the choice of the previous crop (cassava or plantain), in connection with soils and climate constraints and the black Sigatoka caused by Mycosphaerella fijiensis, especially in the Haitian plots ; iv) the crop succession plantain/plantain is the most critical regarding the plantain’s cropping, because whatever the level of intensification, the yields remain relatively low in connection with a degradation of the health state, compared to other previous crops.The driving of an experiment in a research station shows that on the scale of one year, the three tested innovative practices allow maintaining a good soils quality. Healthy plants "PIF" have a better health state (absence of plant parasitic nematodes in the roots) which helps a significant increase of the yields. Cover-crop P. notatum helps the weeds and the soil pests control and favors the improvement of soil biological activity and plantain yields. Worms’ compost contributes to the maintenance of a better soils quality while allowing the regulation of the populations of plant-parasitic nematodes of the plantains.

http://www.theses.fr/2014AGUY0758/document

Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : International audience
Activation of cell signaling by reactive chemicals and pollutants is an important issue for human health. It has been shown that lipophilic nitro-benzoxadiazole (NBD) compounds rapidly move across the plasma membrane and enhance Epidermal Growth Factor Receptor (EGFR) tyrosine phosphorylation in cancer cells. Unlike ligand-dependent activation, the mechanism of this induction relies on the generation of hydrogen peroxide, which is involved in the activation of the catalytic site of the receptor and the inactivation of protein tyrosine phosphatase PTP-1B. Production of H2O2 during redox transformation of NBD compounds is associated with the transition of a monomeric form of Cu/Zn superoxide dismutase 1 (SOD1) to stable dimers. The highly stable and functionally active SOD1 dimer, in the absence of adequate activities in downstream reactions, promotes the disproportionate production and accumulation of intracellular hydrogen peroxide shortly after exposure to NBD compounds. The intrinsic fluorescence of small compounds was used to demonstrate their binding to SOD1. Our data indicate that H2O2 and concomitantly generated electrophilic intermediates behave as independent entities, but all contribute to the biological reactivity of NBD compounds. This study opens a promising path to identify new biomarkers of oxidative/electrophilic stress in the progression of cancer and other diseases
ISSN: 2045-2322

hal-01279094
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01279094
DOI : 10.1038/srep21088
PUBMED : 26883293

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
BACKGROUND: Studies relating long-term exposure to persistent organochlorine pollutants (POPs) with endocrine activities (endocrine disrupting chemicals) on circulating levels of steroid hormones have been limited to a small number of hormones and reported conflicting results. OBJECTIVE: We examined the relationship between serum concentrations of dehydroepiandrosterone, dehydroepiandrosterone sulphate, androstenedione, androstenediol, testosterone, free and bioavailable testosterone, dihydrotestosterone, estrone, estrone sulphate, estradiol, sex-hormone binding globulin, follicle-stimulating hormone, and luteinizing hormone as a function of level of exposure to three POPs known to interfere with hormone-regulated processes in different way: dichlorodiphenyl dichloroethene (DDE), polychlorinated biphenyl (PCB) congener 153, and chlordecone. METHODS: We collected fasting, morning serum samples from 277 healthy, non obese, middle-aged men from the French West Indies. Steroid hormones were determined by gas chromatography-mass spectrometry, except for dehydroepiandrosterone sulphate, which was determined by immunological assay, as were the concentrations of sex-hormone binding globulin, follicle-stimulating hormone and luteinizing hormone. Associations were assessed by multiple linear regression analysis, controlling for confounding factors, in a backward elimination procedure, in multiple bootstrap samples. RESULTS: DDE exposure was negatively associated to dihydrotestosterone level and positively associated to luteinizing hormone level. PCB 153 was positively associated to androstenedione and estrone levels. No association was found for chlordecone. CONCLUSIONS: These results suggested that the endocrine response pattern, estimated by determining blood levels of steroid hormones, varies depending on the POPs studied, possibly reflecting differences in the modes of action generally attributed to these compounds. It remains to be investigated whether this response pattern is predictive of the subsequent occurrence of disease.
ISSN: 1932-6203

hal-00876025
https://hal.archives-ouvertes.fr/hal-00876025
https://hal.archives-ouvertes.fr/hal-00876025/document
https://hal.archives-ouvertes.fr/hal-00876025/file/Persistent_Organochlorine-accepted.pdf
DOI : 10.1371/journal.pone.0066460

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
Accumulating evidence suggests that developmental exposure to environmental chemicals may modify the course of brain development, ultimately leading to neuropsychiatric / neurodegenerative disorders later in life. In the present study, we assessed the impact of one of the most frequently used pesticides in both residential and agricultural applications - the synthetic pyrethroid cypermethrin (CYP) - on developmental neurotoxicity (DNT). Female mice were perinatally exposed to low doses of CYP (5 and 20 mg/kg body weight) from gestation to postnatal day 15. Behavioral analyses were performed during the offspring's early life and during adulthood. Postnatal analyses revealed that perinatal exposure to CYP disturbed motor development without modifying sensory and communicative skills. We found that later in life, CYP-exposed offspring expressed maladaptive behaviors in response to highly challenging tasks and abnormal sociability. Transcriptomic analyses performed in the offspring's brain at the end of the exposure, highlighted mitochondrial dysfunction as a relevant pathomechanism underlying CYP-induced DNT. Interestingly, several genes involved in proteostasis maintenance were also shown to be dysregulated suggesting that alterations in biogenesis, folding, trafficking and degradation of proteins may significantly contribute to CYP-related DNT. From a regulatory perspective, this study highlights that behavioral and transcriptomic analyses are complementary tools providing useful direction for better DNT characterization, and as such, should be used together more systematically.
ISSN: 1932-6203

hal-01616489
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01616489
DOI : 10.1371/journal.pone.0184475
PUBMED : 29020013

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Aryl hydrocarbon receptor-dependent genomic effects of environmental polycyclic aromatic hydrocarbons (PAHs) have been shown to be modulated by non-genomic protein kinase C (PKC)-related pathways. The present study was designed to determine whether PKC activation may also impair estrogenic genomic response triggered by PAHs. Treatment by the PKC activator phorbol 12-myristate 13-acetate (PMA) was found to markedly and differentially impair the up-regulation of estrogenic markers triggered by the estrogenic PAH benzanthracene (BZA) in cultured human mammary cells; BZA-mediated mRNA up-regulation of pS2 and amphiregulin was thus increased, whereas that of progesterone receptor and CXCL12 was repressed. BZA/PMA cotreatment however failed to alter BZA-mediated increase of activity of a luciferase gene reporter construct driven by an estrogen response element, thus discarding any global effect of PMA toward BZA-triggered estrogen receptor activation. Various chemicals inhibiting PKCs or extracellular signal-regulated kinase (ERK) as well as the knock-down of PKCδ expression counteracted the PMA-mediated increase of pS2 mRNA up-regulation triggered by BZA, demonstrating that it was dependent on PKCs, including PKCδ isoform, and ERKs. This non-genomic modulation of estrogenic effects of PAHs by PKC activation may have to be considered when considering the deleterious effects of these environmental contaminants towards the endocrine system.
ISSN: 0887-2333

inserm-00872862
http://www.hal.inserm.fr/inserm-00872862
DOI : 10.1016/j.tiv.2012.05.006
PUBMED : 22643241

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Recently it has become clear that exposure to xenobiotics may result in various forms of cell death; not only passive cell deaths like necrosis, or programmed cell deaths such as apoptosis, but also regulated necrosis, autophagy, senescence, or mitotic catastrophe. Complex cell signaling networks influence the processing of cell death. Furthermore, recent research has revealed early complex molecular interactions between organelles prior to the final triggering of cell death. The plasma membrane may play an important role in the early cell death signaling events. Regarding this latter aspect, drugs and environmental pollutants have been reported to affect plasma membrane characteristics which may further affect cell fate. Changes in membrane fluidity or in composition and function of specialized membrane microdomains (plasma membrane remodeling) have been proven to be involved in the regulation of many important physiological signaling pathways, including cell death. Furthermore, it has been suggested that a crosstalk between chemical-induced cellular membrane effects and other organelles may be of vital importance to explain the final outcome of chemical exposure. Here, we review the effects of plasma membrane remodeling on cell survival and cell death; we describe how the cell signaling pathways activated by changes in plasma membrane characteristics may influence cell fate. Since plasma membrane function plays an important role in the regulation of a number of cellular responses, it has been implicated in the development or progress of several diseases. A better knowledge of the effects of various chemicals on plasma membrane remodeling may be important for understanding the pathogenesis of major diseases, and may assist in developing new therapeutic strategies.
ISSN: 0300-483X

inserm-00818916
http://www.hal.inserm.fr/inserm-00818916
DOI : 10.1016/j.tox.2012.12.014
PUBMED : 23287390

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
CXCL-test is a method that uses the estrogen-dependent secretion of the natural endogenous chemokine CXCL12 to evaluate the estrogenic activity of molecules. CXCL12 chemokine is involved in the estrogen dependent proliferation of breast cancer cells. Its measure is an indicator of cell proliferation and is used as an alternative test to classical proliferation test. Here we aimed to optimize this test, first to increase the number of tested molecules in a single assay and then to decrease the number of intermediate steps. The optimized CXCL-test was finally used for the evaluation of the estrogenic potency of emerging chemical pollutants: the UV filter benzophenones (BPs). The effect of BPs on CXCL12 secretion was also validated by real time quantitative RT-PCR. The optimized CXCL-test allowed a fast and direct assessment of estrogenic potency of molecules. The estrogenic activities of benzophenones were characterized and divided in two groups. The first one contains weak estrogenic compounds (BP, BP1, BP2, BP3, 234BP and 2344′BP). The second one contains medium estrogenic compounds (4BP, 44′BP, BP8, THB).
ISSN: 0045-6535

hal-01477205
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01477205
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01477205/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01477205/file/Rapid%20assessment%20of%20estrogenic%20compounds_accepted.pdf
DOI : 10.1016/j.chemosphere.2017.01.037

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
BACKGROUND: The aryl hydrocarbon receptor (AhR) has gradually emerged as a regulator of inflammation in the lung and other tissues. AhR may interact with the p65-subunit of the nuclear factor (NF)-κB transcription factors, but reported outcomes of AhR/NF-κB-interactions are conflicting. Some studies suggest that AhR possess pro-inflammatory activities while others suggest that AhR may be anti-inflammatory. The present study explored the impact of AhR and its binding partner AhR nuclear translocator (Arnt) on p65-activation and two differentially regulated chemokines, CXCL8 (IL-8) and CCL5 (RANTES), in human bronchial epithelial cells (BEAS-2B). RESULTS: Cells were exposed to CXCL8- and CCL5-inducing chemicals, 1-nitropyrene (1-NP) and 1-aminopyrene (1-AP) respectively, or the synthetic double-stranded RNA analogue, polyinosinic-polycytidylic acid (Poly I:C) which induced both chemokines. Only CXCL8, and not CCL5, appeared to be p65-dependent. Yet, constitutively active unligated AhR suppressed both CXCL8 and CCL5, as shown by siRNA knock-down and the AhR antagonist α-naphthoflavone. Moreover, AhR suppressed activation of p65 by TNF-α and Poly I:C as assessed by luciferase-assay and p65-phosphorylation at serine 536, without affecting basal p65-activity. In contrast, Arnt suppressed only CXCL8, but did not prevent the p65-activation directly. However, Arnt suppressed expression of the NF-κB-subunit RelB which is under transcriptional regulation by p65. Furthermore, AhR-ligands alone at high concentrations induced a moderate CXCL8-response, without affecting CCL5, but suppressed both CXCL8 and CCL5-responses by Poly I:C. CONCLUSION: AhR and Arnt may differentially and independently regulate chemokine-responses induced by both inhaled pollutants and pulmonary infections. Constitutively active, unligated AhR suppressed the activation of p65, while Arnt may possibly interfere with the action of activated p65. Moreover, ligand-activated AhR suppressed CXCL8 and CCL5 responses by other agents, but AhR ligands alone induced CXCL8 responses when given at sufficiently high concentrations, thus underscoring the duality of AhR in regulation of inflammation. We propose that AhR-signaling may be a weak activator of p65-signaling that suppresses p65-activity induced by strong activators of NF-κB, but that its anti-inflammatory properties also are due to interference with additional pathways.
ISSN: 1478-811X

inserm-01085082
http://www.hal.inserm.fr/inserm-01085082
http://www.hal.inserm.fr/inserm-01085082/document
http://www.hal.inserm.fr/inserm-01085082/file/s12964-014-0048-8.pdf
PUBMED : 25201625