Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Polycyclic aromatic hydrocarbons (PAHs), such as benzo[a]pyrene (B[a]P), are widely distributed environmental contaminants exerting toxic effects such as genotoxicity and carcinogenicity, mainly associated with aryl hydrocarbon receptor (AhR) activation and the subsequent induction of cytochromes P-450 (CYP) 1-metabolizing enzymes. We previously reported an up-regulation of AhR expression and activity in primary cultures of human T lymphocyte by a physiological activation. Despite the suggested link between exposure to PAHs and the risk of lymphoma, the potential of activated human T lymphocytes to metabolize AhR exogenous ligands such as B[a]P, and produce DNA damage has not been investigated. In the present study, we characterized the genotoxic response of primary activated T lymphocytes to B[a] P. We demonstrated that, following T lymphocyte activation, B[a]P treatment triggers a marked increase in CYP1 expression and activity generating, upon metabolic activation, DNA adducts and double-strand breaks (DSBs) after a 48-h treatment. At this time point, B[a]P also induces a DNA damage response with ataxia telangiectasia mutated kinase activation, thus producing a p53-dependent response and T lymphocyte survival. B[a]P activates DSB repair by mobilizing homologous recombination machinery but also induces gene mutations in activated human T lymphocytes which could consequently drive a cancer process. In conclusion, primary cultures of activated human T lymphocytes represent a good model for studying genotoxic effects of environmental contaminants such as PAHs, and predicting human health issues.
ISSN: 0006-2952

hal-01560145
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01560145
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01560145/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01560145/file/Liamin%20et%20al.%20-%20Benzo%5Ba%5Dpyrene-induced%20DNA%20damage%20associated%20with%20.pdf
DOI : 10.1016/j.bcp.2017.04.025

Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : International audience
Most tumors undergo metabolic reprogramming towards glycolysis, the so-called Warburg effect, to support growth and survival. Overexpression of IF1, the physiological inhibitor of the F0F1ATPase, has been related to this phenomenon and appears to be a relevant marker in cancer. Environmental contributions to cancer development are now widely accepted but little is known about the underlying intracellular mechanisms. Among the environmental pollutants humans are commonly exposed to, benzo[a]pyrene (B[a]P), the prototype molecule of polycyclic aromatic hydrocarbons (PAHs), is a well-known human carcinogen. Besides apoptotic signals, B[a]P can also induce survival signals in liver cells, both likely involved in cancer promotion. Our previous works showed that B[a]P elicited a Warburg-like effect, thus favoring cell survival. The present study aimed at further elucidating the molecular mechanisms involved in the B[a]P-induced metabolic reprogramming, by testing the possible involvement of IF1. We presently demonstrate, both in vitro and in vivo, that PAHs, especially B[a]P, strongly increase IF1 expression. Such an increase, which might rely on β2-adrenergic receptor activation, notably participates to the B[a]P-induced glycolytic shift and cell survival in liver cells. By identifying IF1 as a target of PAHs, this study provides new insights about how environmental factors may contribute to related carcinogenesis.
ISSN: 2045-2322

hal-01518808
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01518808
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01518808/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01518808/file/Hardonni%C3%A8re%20et%20al%202017.pdf
DOI : 10.1038/s41598-017-00269-7

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
The contamination of indoor environments with chemical compounds released by materials and furniture, such as semi-volatile organic compounds (SVOCs) is less documented in schools than in dwellings - yet children spend 16% of their time in schools, where they can also be exposed. This study is one of the first to describe the contamination of the air and dust of 90 classrooms from 30 nursery and primary schools by 55 SVOCs, including pesticides, phosphoric esters, musks, polycyclic aromatic hydrocarbons (PAHs), polychlorobiphenyls (PCBs), phthalates and polybromodiphenylethers (PBDEs). Air samples were collected using an active sampling method, and dust samples were collected via two sampling methods (wiping and vacuum cleaning). In air, the highest concentrations (median extbackslashtextgreater 100 ng/m(3) ) were measured for diisobutyl-phthalate (DiBP), dibutyl-phthalate (DBP), diethyl-phthalate (DEP), bis(2-ethylhexyl)-phthalate (DEHP) and galaxolide. In dust, the highest concentrations (median extbackslashtextgreater 30 μg/g) were found for DEHP, diisononyl-phthalate (DiNP), DiBP and DBP. An attempt to compare two floor dust sampling methods using a single unit (ng/m²) was carried out. SVOC concentrations were higher in wiped dust, but frequencies of quantification were greater in vacuumed dust.
ISSN: 0905-6947

hal-01286254
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01286254
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01286254/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01286254/file/Semi-volatile%20organic%20compounds%20in%20the%20air%20and%20dust_accepted.pdf
DOI : 10.1111/ina.12288

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 Elsevier
Résumé : International audience
People are exposed to multiple pollutants, especially indoors. In the perspective of a cumulative risk assessment, a multi-residue analytical method was developed to assess the contamination of indoor suspended particulate matter by 55 semi-volatile organic compounds (SVOCs) including musk fragrances, organochlorines (OCs), organophosphates (OPs), polycyclic aromatic hydrocarbons (PAHs), polybromodiphenylethers (PBDEs), polychlorobiphenyls (PCBs), phthalates and pyrethroids. It is based on thermal desorption (TD) coupled with gas chromatography/mass spectrometry (GC/MS). Once the thermal desorption conditions were optimized, the method was validated in terms of quantification limits and accuracy using a standard reference material (SRM 2585). Instrumental quantification limits were 10pg (some OCs, some pyrethroids, musk fragrances, OPs, PAHs, PBDEs and PCBs), 100pg (phthalates and other OCs) and 1000pg (other pyrethroids) corresponding respectively to method quantification limits of 1, 10, and 100pg/m(3) for a sampled air volume of 20m(3). Calibration quadratic curves for ranges of 10-1000, 100-10,000, and 1000-100,000pg, depending on the substance, exhibit determination coefficients above 0.999. Recoveries were between 61 and 96% for chlorinated pesticides, PAHs, PBDEs and PCBs present in the SRM 2585. A test of the method on indoor particulate matter samples (PM(10)) collected on quartz fiber filters in French dwellings demonstrated its ability to quantify SVOCs from a small amount of PM.
ISSN: 0021-9673

hal-00732133
https://hal.archives-ouvertes.fr/hal-00732133
DOI : 10.1016/j.chroma.2012.07.025
PUBMED : 22840824

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
The heterodimeric L-type amino acid transporter (LAT) 1/ CD98hc is overexpressed in lung cancers with a poor prognosis factor. Factors that contribute to LAT1/CD98hc overexpression in lung cells remain however to be determined, but the implication of atmospheric pollution can be suspected. The present study was therefore designed to analyze the effects of diesel exhaust particle (DEP) extract (DEPe) on LAT1/CD98hc expression in bronchial epithelial BEAS-2B cells. Exposure to DEPe up-regulated LAT1 and CD98hc mRNA levels in a concentration-dependent manner, with DEPe EC50 values (around 0.2 μg/mL) relevant to environmental situations. DEPe concomitantly induced LAT1/CD98hc protein expression and LAT1-mediated leucine accumulation in BEAS-2B cells. Inhibition of the aryl hydrocarbon receptor (AhR) pathway through the use of a chemical AhR antagonist or the siRNA-mediated silencing of AhR expression was next found to prevent DEPe-mediated induction of LAT1/CD98hc, indicating that this regulation depends on AhR, known to be activated by major chemical DEP components like polycyclic aromatic hydrocarbons. DEPe exposure was finally shown to induce mRNA expression and activity of matrix metalloproteinase (MMP)-2 in BEAS-2B cells, in a CD98hc/focal adhesion kinase (FAK)/extracellular regulated kinase (ERK) manner, thus suggesting that DEPe-mediated induction of CD98hc triggers activation of the integrin/FAK/ERK signaling pathway known to be involved in MMP-2 regulation. Taken together, these data demonstrate that exposure to DEPe induces functional overexpression of the amino acid transporter LAT1/CD98h in lung cells. Such a regulation may participate to pulmonary carcinogenic effects of DEPs, owing to the well-documented contribution of LAT1 and CD98hc to cancer development.
ISSN: 0041-008X

hal-01237095
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01237095
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01237095/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01237095/file/Aryl%20hydrocarbon%20receptor-dependent%20up-regulation_accepted.pdf
DOI : 10.1016/j.taap.2015.11.014

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Particle/gas and dust/gas partition coefficients (Kp and Kd) are two key parameters that address the partitioning of semi-volatile organic compounds (SVOCs) between gas-phase, airborne particles, and settled dust in indoor environment. A number of empirical equations to calculate the values of Kp and Kd have been reported in the literature. Therefore, the difficulty lies in the selection of a specific empirical equation in a given situation. In this study, we retrieved from the literature 38 empirical equations for calculating Kp and Kd values from the SVOC saturation vapor pressure and octanol/air partition coefficient. These values were calculated for 72 SVOCs: 9 phthalates, 9 polybrominated diphenyl ethers (PBDEs), 11 polychlorinated biphenyls (PCBs), 22 biocides, 14 polycyclic aromatic hydrocarbons (PAHs), 3 alkylphenols, 2 synthetic musks, tributylphosphate, and bisphenol A. The mean and median values of log10 Kp or log10 Kd for most SVOCs were of the same order of magnitude. The distribution of log10 Kp values was fitted to either a normal distribution (for 27 SVOCs) or a log-normal distribution (for 45 SVOCs). This work provides a reference distribution of the log10 Kp for 72 SVOCs, and its use may reduce the bias associated with the selection of a specific value or equation
ISSN: 0045-6535

hal-01295671
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01295671
DOI : 10.1016/j.chemosphere.2016.03.007
PUBMED : 27016817

Éditeur(s) : HAL CCSD
Résumé : International audience
Objective: To estimate the social cost of respiratory cancers attributable to occupational risk factors in France in 2010. Methods: We estimated the number of cases ofrespiratory cancers attributable to each identified occupational risk factor according to the attributable fractions method. We also estimated direct (costs of hospital stays, drugs, outpatient care) and indirect costs (production losses) related to morbidity (absenteeism and presenteeism) and mortality (years of lost production). Production losses for paid work and unpaid domestic activities were taken into account. Results: The social cost of respiratory cancers (lung, larynx, sinonasal, pleural mesothelioma) attributable to exposure to asbestos, chromium, diesel engine exhaust, polycyclic aromatic hydrocarbons, painting occupations (unidentified carcinogen), crystalline silica, wood and leather dust in France in 2010 was estimated to be between 960 and 1,866 million. The cost of lung cancer represents between 804 and 1,617 million. The three risk factors with the greatest impact are asbestos ((sic)530 to 890 million), diesel engine exhaust ((sic)227 to 394 million), and crystalline silica ( 116 to 268 million). Conclusion: These results provide a conservative estimate of the public health and economic burden of respiratory cancers attributable to occupational risk factors from a societal perspective.
ISSN: 0995-3914

hal-01659246
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01659246
DOI : 10.3917/spub.174.0509
PUBMED : 29034666

Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : International audience
Exposure to environmental polycyclic aromatic hydrocarbons (PAHs), such as benzo(a) pyrene (B(a) P), has been linked to several health-threatening risks. PAHs were also shown to hinder adrenergic receptor (ADR) responses. As we previously demonstrated that Ba) P can directly interact with the beta 2ADR, we investigated here whether B(a) P could decrease beta 2ADR responsiveness by triggering receptor desensitization phenomena. We firstly showed that exposure to B(a) P reduced beta 2ADRmediated epinephrine-induced induction of NR4A gene mRNAs and of intracellular cAMP. Analysis of beta 2ADR protein expression demonstrated that B(a) P rapidly decreased membrane expression of beta 2ADR with a subsequent degradation of receptor protein. B(a) P exposure concomitantly rapidly increased the beta 2ADR mRNA levels. The use of the beta-blockers, propranolol and ICI 118.551, demonstrated the involvement of beta 2ADR itself in this increase. However, sustained exposure to Ba) P induced a diminution of beta 2ADR mRNA steady-state as a result of the acceleration of its degradation. Together, these results show that, beside the well-known activation of the aryl hydrocarbon receptor, PAH deleterious effects may involve the dysfunction of adrenergic responses through, in part, the desensitization of beta 2ADR. This may be taken in consideration when beta 2-agonists/antagonists are administered in patients exposed to important concentrations of PAHs, e.g. in cigarette smokers.
ISSN: 2045-2322

hal-01560151
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01560151
DOI : 10.1038/s41598-017-03646-4
PUBMED : 28607424

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Plasma membrane is an early target of polycyclic aromatic hydrocarbons (PAH). We previously showed that the PAH prototype, benzo[a]pyrene (B[a]P), triggers apoptosis via DNA damage-induced p53 activation (genotoxic pathway) and via remodeling of the membrane cholesterol-rich microdomains called lipid rafts, leading to changes in pH homeostasis (non-genotoxic pathway). As omega-3 (n-3) fatty acids can affect membrane composition and function or hamper in vivo PAH genotoxicity, we hypothesized that addition of physiologically relevant levels of polyunsaturated n-3 fatty acids (PUFAs) might interfere with B[a]P-induced toxicity. The effects of two major PUFAs, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), were tested on B[a]P cytotoxicity in the liver epithelial cell line F258. Both PUFAs reduced B[a]P-induced apoptosis. Surprisingly, pre-treatment with DHA increased the formation of reactive B[a]P metabolites, resulting in higher levels of B[a]P-DNA adducts. EPA had no apparent effect on B[a]P metabolism or related DNA damage. EPA and DHA prevented B[a]P-induced apoptotic alkalinization by affecting Na(+)/H(+) exchanger 1 activity. Thus, the inhibitory effects of omega-3 fatty acids on B[a]P-induced apoptosis involve a non-genotoxic pathway associated with plasma membrane remodeling. Our results suggest that dietary omega-3 fatty acids may have marked effects on the biological consequences of PAH exposure.
ISSN: 0009-2797

hal-00950341
https://hal.archives-ouvertes.fr/hal-00950341
https://hal.archives-ouvertes.fr/hal-00950341/document
https://hal.archives-ouvertes.fr/hal-00950341/file/DENDELE_et_al_2013-unmarked.pdf
PUBMED : 24246761

Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : International audience
Cancer cells display alterations in many cellular processes. One core hallmark of cancer is the Warburg effect which is a glycolytic reprogramming that allows cells to survive and proliferate. Although the contributions of environmental contaminants to cancer development are widely accepted, the underlying mechanisms have to be clarified. Benzo[a]pyrene (B[a]P), the prototype of polycyclic aromatic hydrocarbons, exhibits genotoxic and carcinogenic effects, and it is a human carcinogen according to the International Agency for Research on Cancer. In addition to triggering apoptotic signals, B[a]P may induce survival signals, both of which are likely to be involved in cancer promotion. We previously suggested that B[a]P-induced mitochondrial dysfunctions, especially membrane hyperpolarization, might trigger cell survival signaling in rat hepatic epithelial F258 cells. Here, we further characterized these dysfunctions by focusing on energy metabolism. We found that B[a]P promoted a metabolic reprogramming. Cell respiration decreased and lactate production increased. These changes were associated with alterations in the tricarboxylic acid cycle which likely involve a dysfunction of the mitochondrial complex II. The glycolytic shift relied on activation of the Na+/H+ exchanger 1 (NHE1) and appeared to be a key feature in B[a]P-induced cell survival related to changes in cell phenotype (epithelial-to-mesenchymal transition and cell migration).
ISSN: 2045-2322

Droits : http://creativecommons.org/licenses/by/
hal-01359569
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01359569
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01359569/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01359569/file/The%20environmental%20carcinogen-CCBY%20%281%29.pdf
DOI : 10.1038/srep30776

Éditeur(s) : HAL CCSD
Résumé : International audience
Environmental context The safeguarding of water supplies and drinking water is a major issue when considering human health risk management. In this context, an automatic and on-site fractionation system for the detection of organic contaminants has been developed. The main goal of this system is to establish an initial diagnosis by identifying a class of substances involved in a case of pollution. Abstract This paper proposes a new approach for the preconcentration, fractionation, prediction and detection of organic micropollutants in water. The main aim of this study was to implement an innovative fractionation method and a prediction model based on the physicochemical properties of compounds and interactions with the sorbent of solid-phase extraction cartridges. Two sorbents (Strata-SAX and Oasis-HLB) and three specific eluting solvents (mixture of methanol and sodium chloride and mixtures of acetonitrile and ultrapure water) were used to separate organic compounds into five specific fractions according to their physicochemical properties (anionic and cationic or neutral compounds with various polarity). More than 75 molecules (43 molecules individually studied and a mixture with 43 molecules, including 11 molecules individually studied) including pesticides, pharmaceuticals, endocrine disruptors and polycyclic aromatic hydrocarbons, with various properties were studied, and the results showed that the elution fraction can be predicted for more than 85% of the compounds. This methodology could simplify the analytical chain by reducing detailed analysis on limited categories of compounds, and could be used for a rapid and on-site screening of organic compounds. © CSIRO 2016.
Environmental Chemistry

hal-01373945
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01373945
DOI : 10.1071/EN15135

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Recent research has demonstrated the importance of dermal exposure for some semivolatile organic compounds (SVOCs) present in the gas phase of indoor air. Though models for estimating dermal intake from gaseous SVOCs exist, their predictions can be subject to variations in input parameters, which can lead to large variation in exposure estimations. In this sensitivity analysis for a steady state model, we aimed to assess these variations and their determinants using probabilistic Monte Carlo sampling for 8 SVOCs from different chemical families: phthalates, bisphenols, polycyclic aromatic hydrocarbons (PAHs), organophosphorus (OPs), organochlorines (OCs), synthetic musks, polychlorinated biphenyls (PCBs) and polybromodiphenylethers (PBDEs). Indoor SVOC concentrations were found to be the most influential parameters. Both Henry's law constant (H) and octanol/water partition coefficient (Kow) uncertainty also had significant influence. While exposure media properties such as volume fraction of organic matter in the particle phase (fom-part), particle density (ρpart), concentration ([TSP]) and transport coefficient (ɣd) had a slight influence for some compounds, human parameters such as body weight (W), body surface area (A) and daily exposure (t) make a marginal or null contribution to the variance of dermal intake for a given age group. Inclusion of a parameter sensitivity analysis appears essential to reporting uncertainties in dermal exposure assessment.
ISSN: 0160-4120

hal-01526430
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01526430
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01526430/file/Dermal%20absorption%20of%20semivolatile%20organic%20compounds_accepted.pdf
DOI : 10.1016/j.envint.2017.02.005
PUBMED : 28249739