Publications by authors named "Sylvain Billet"

31 Publications

The toxicity of SiO NPs on cell proliferation and cellular uptake of human lung fibroblastic cell line during the variation of calcination temperature and its modeling by artificial neural network.

J Environ Health Sci Eng 2021 Jun 30;19(1):985-995. Epub 2021 Apr 30.

UR4492, Unité de Chimie Environnementale et Interactions sur le Vivant, SFR Condorcet FR CNRS 3417, Université du Littoral Côte d'Opale, Dunkerque, France.

Less attention had been paid to cell toxicity of the various synthesis methods of nanoparticles, this study investigated the effect of the calcination temperature(CT) on the crystallization of SiO nanoparticles(NPs), cell proliferation(CP), and cellular uptake(CU) in MRC-5. In this study, parameters were adjusted as CT(70-1000 °C), calcination time(2, 12, and 24 h), and catalyst feed rate(0.01, 0.05, and 0.1 mL.min). CP was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) test after a 24-h exposure. The CU was achieved using ICP-MS. Results were analyzed using MATLAB2018. Results revealed that the size of synthesized particles was lower than 50 nm and, the XRD peak varied from 21 to 30° during the increase in CT. FTIR spectra confirmed the existence of Si-O and Si-Cl bonds. The maximum level of crystallization was at 1000 °C. CP decreased with the rise in the concentration of NPs( < 0.05), as well as an increase in feed rate. A positive relationship between increased crystallization and decreased CP(R = 0.78) was seen, while such a trend was not observed in calcination time. The suggested structure in this study was 4:10:1 with R = 0.97, R = 0.97, RMSE = 0.25, and MSE = 0.003. Furthermore, the CU rate increased with the rise in CT and calcination time. The maximum and minimum CU levels were related to NPs calcinated in 1000 °C-24 h and 350 °C-2 h, respectively. As a consequence, the most toxicity of SiO NPs was related to the crystalline NP. Therefore, the increase in CT and the calcination time were significant factors affecting on crystallization of SiO NPs, CP of lung cell, as well as CU of SiO.

Supplementary Information: The online version contains supplementary material available at 10.1007/s40201-021-00663-4.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40201-021-00663-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172710PMC
June 2021

Toxicological responses of BEAS-2B cells to repeated exposures to benzene, toluene, m-xylene, and mesitylene using air-liquid interface method.

J Appl Toxicol 2020 Dec 2. Epub 2020 Dec 2.

Unité de Chimie Environnementale et Interactions sur le Vivant, SFR Condorcet FR CNRS 3417, Université du Littoral Côte d'Opale, Dunkirk, France.

In order to reduce exposure to toxic chemicals, the European REACH regulation (1907/2006) recommends substituting toxic molecules with compounds that are less harmful to human health and the environment. Toluene is one of the most frequently used solvents in industries despite its toxicity. The objective of this study is to better understand and compare the toxicity of toluene and its homologues in a bronchial cell model. Thus, human bronchial BEAS-2B cells were exposed to steams of toluene, m-xylene, mesitylene (1,3,5-trimethylbenzene), and benzene (20 and 100 ppm). Exposure was carried out using an air-liquid interface (ALI) system (Vitrocell) during 1 h/day for 1, 3, or 5 days. Cytotoxicity, xenobiotic metabolism enzyme gene expression, and inflammatory response were evaluated following cell exposures. BEAS-2B cell exposure to toluene and its homologues revealed the involvement of major (CYP2E1) and minor metabolic pathways (CYP1A1). A late induction of genes (EPHX1, DHDH, ALDH2, and ALDH3B1) was measured from Day 3 and can be linked to the formation of metabolites. An increase in the secretion level of inflammatory markers (TNF-α, IL-6, IL-8, MCP-1, and GM-CSF) was also observed. In parallel, regulation between inflammatory mediators and the expression of transmembrane glycoprotein mucin MUC1 was also studied. This in vitro approach with ALI system points out the relevance of conducting repeated exposures to detect potential late effects. The difference recorded after cell exposure to toluene and its homologues highlights the importance of substitution principle.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jat.4113DOI Listing
December 2020

Extracellular vesicles as actors in the air pollution related cardiopulmonary diseases.

Crit Rev Toxicol 2020 05 5;50(5):402-423. Epub 2020 Jun 5.

Unit of Environmental Chemistry and Interactions with Life, UCEIV EA4492, SFR Condorcet FR CNRS, University of Littoral Côte d'Opale, Dunkerque, France.

Many associations were reported between air pollution and daily mortality rates for cardiopulmonary diseases. Humans are exposed to a mixture of oxidizing gases and particles, both anthropogenic and natural. Exposure to air toxics causes or exacerbates cardiovascular damages and respiratory diseases. Numerous studies have identified the induction of oxidative stress and sustained inflammatory response as among the main known underlying pathophysiological mechanisms of air pollutants. More recently, the relationship between these mechanisms of action and the secretion of extracellular vesicles (EVs) by lung cells has been revealed. EVs have been shown to be important mediators of cellular communication in the body. The purpose of this review is to first recall the main air pollutants. Then, the cardiopulmonary diseases caused by exposure to air pollution and the pathophysiological mechanisms are presented before showing, through an exhaustive review of the literature, the involvement of EVs in the toxicity of air pollutants and the initiation of cardiopulmonary diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/10408444.2020.1763252DOI Listing
May 2020

A prospective pilot study of the T-lymphocyte response to fine particulate matter exposure.

J Appl Toxicol 2020 05 23;40(5):619-630. Epub 2020 Jan 23.

EA 4492 - UCEIV - Unité de Chimie Environnementale et Interactions sur le Vivant, Université du Littoral Côte d'Opale, SFR Condorcet FR CNRS 3417, Dunkerque, France.

Exposure to air pollution is associated with increased morbidity and mortality. Once the fine atmospheric particulate matter (FP) is inhaled, some of its compounds can pass through the lungs and reach the bloodstream where they can come into contact with immune cells. Exposure to FP particularly affects sensitive populations such as the elderly. Aging affects the immune system, making the elderly more vulnerable. The project aims to determine the effects of FP exposure on human T cells while looking for biomarkers associated with exposure. Blood samples from 95 healthy subjects in three different age groups (20-30, 45-55 and 70-85 years) were collected to determine a potential age effect. T lymphocytes were isolated to be exposed ex vivo for 72 hours to 45 μg/mL of FP collected in Dunkirk and chemically characterized. Overexpression of the CYP1A1, CYP1B1 and CYP2S1 genes was therefore measured after exposure of the T cells to FP. These genes code for enzymes known to be involved in the metabolic activation of organic compounds such as polycyclic aromatic hydrocarbons detected in the FP sample. T-cell profiling allowed us to suggest a mixed T-helper 1/2 profile caused by exposure to FP. With regard to the influence of age, we have observed differences in the expression of certain genes, as well as an increase in interleukin-4 and -13 concentrations in the elderly. These results showed that exposure of T lymphocytes to FP causes effects on both transcriptomic and cytokine secretion levels.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jat.3932DOI Listing
May 2020

In vitro toxicological evaluation of emissions from catalytic oxidation removal of industrial VOCs by air/liquid interface (ALI) exposure system in repeated mode.

Toxicol In Vitro 2019 Aug 22;58:110-117. Epub 2019 Mar 22.

UCEIV - EA4492, Unité de Chimie Environnementale et Interactions sur le Vivant, SFR Condorcet FR CNRS 3417, Université du Littoral Côte d'Opale, Dunkerque, France.

Toxicity of toluene and by-products formed during its catalytic oxidative degradation was studied in human bronchial BEAS-2B cells repeatedly exposed. BEAS-2B cells were exposed using an Air-Liquid Interface (ALI) System (Vitrocell®) for 1 h per day during 1, 3 or 5 days to gaseous flows: toluene vapors (100 and 1000 ppm) and outflow after catalytic oxidation of toluene (10 and 100%). After exposure to gaseous flow, cytotoxicity, inflammatory response and Xenobiotic Metabolism Enzymes (XME) gene expression were investigated. No significant cytotoxicity was found after 5 days for every condition of exposure. After cells exposure to catalytic oxidation flow, IL-6 level increased no significantly in a time- and dose-dependent way, while an inverted U-shaped profile of IL-8 secretion was observed. XME genes induction, notably CYP2E1 and CYP2F1 results were in line with the presence of unconverted toluene and benzene formed as a by-product, detected by analytical methods. Exposure to pure toluene also demonstrated the activation of these XMEs involved in its metabolism. Repeated exposure permits to show CYP1A1, CYP1B1 and CY2S1 expression, probably related to the formation of other by-products, as PAHs, not detected by standard analytical methods used for the development of catalysts.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.tiv.2019.03.030DOI Listing
August 2019

Chemical characterization of fine and ultrafine PM, direct and indirect genotoxicity of PM and their organic extracts on pulmonary cells.

J Environ Sci (China) 2018 Sep 27;71:168-178. Epub 2018 Apr 27.

University of the Littoral Opal Coast, Unit of Environmental Chmistry and Interactions with Living Organisms, UCEIV EA4492, SFR Condorcet FR CNRS 3417, Dunkerque, France.

Particulate matter in ambient air constitutes a complex mixture of fine and ultrafine particles composed of various chemical compounds including metals, ions, and organics. A multidisciplinary approach was developed by studying physico-chemical characteristics and mechanisms involved in the toxicity of particulate atmospheric pollution. PM and PM including ultrafine particles were sampled in Dunkerque, a French industrialized seaside city. PM samples were characterized from a chemical and toxicological point of view. Physico-chemical characterization evidenced that PM comes from several sources: natural ones, such as soil resuspension and marine sea-salt emissions, as well as anthropogenic ones, such as shipping traffic, road traffic, and industrial activities. Human BEAS-2B lung cells were exposed to PM, or to the Extractable Organic Matter (EOM) of PM and PM. These exposures induced several mechanisms of action implied in the genotoxicity, such as oxidative DNA adducts and DNA Damage Response. The toxicity of PM-EOM was higher for the sample including the ultrafine fraction (PM) containing also higher concentrations of polycyclic aromatic hydrocarbons. These results evidenced the major role of organic compounds in the toxicity of PM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jes.2018.04.022DOI Listing
September 2018

Influence of aging in the modulation of epigenetic biomarkers of carcinogenesis after exposure to air pollution.

Exp Gerontol 2018 09 31;110:125-132. Epub 2018 May 31.

Unité de Chimie Environnementale et Interactions sur le Vivant (EA4492), Université du Littoral Côte d'Opale, Dunkerque 59140, France.

Background: Classified as carcinogenic to humans by the IARC in 2013, fine air particulate matter (PM) can be inhaled and retained into the lung or reach the systemic circulation. This can cause or exacerbate numerous pathologies to which the elderly are often more sensitive.

Methods: In order to estimate the influence of age on the development of early cellular epigenetic alterations involved in carcinogenesis, peripheral blood mononuclear cells sampled from 90 patients from three age classes (25-30, 50-55 and 75-80 years old) were ex vivo exposed to urban PM.

Results: Particles exposure led to variations in telomerase activity and telomeres length in all age groups without any influence of age. Conversely, P16 gene expression increased significantly with age after exposure to PM. Age could enhance MGMT gene expression after exposure to particles, by decreasing the level of promoter methylation in the oldest people.

Conclusion: Hence, our results demonstrated several tendencies in cells modification depending on age, even if all epigenetic assays were carried out after a limited exposure time allowing only one or two cell cycles. Since lung cancer symptoms appear only at an advanced stage, our results underline the needs for further investigation on the studied biomarkers for early diagnosis of carcinogenesis to improve survival.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.exger.2018.05.018DOI Listing
September 2018

A new approach for safe planning transfer using semi-automatically adjustable instrument guides.

Int J Med Robot 2018 Aug 30;14(4):e1907. Epub 2018 Mar 30.

Chair of Medical Engineering, RWTH Aachen.

Accurate planning transfer is a prerequisite for successful operative care. For different applications, diverse computer-assisted systems have been developed and clinically evaluated. This paper presents the implementation and evaluation of a new modular concept. The approach is based on passive application specific kinematics that are semi-automatically adjusted using a universal hand-held computer controlled Smart Screw Driver. The system was realized for pedicle screw instrumentation and evaluated according to IEC 60601-1-6 (usability engineering). The accuracies of the drill holes achieved were comparable with robotic approaches, while operation time and radiation were reduced compared with conventional operation techniques. The adjustment procedure has proven high learnability and user satisfaction. The next step will be optimization of the kinematic structure and fixation to the patient in order to increase accuracies of planning transfer as well as evaluation of the overall system by medical staff in preclinical and clinical studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/rcs.1907DOI Listing
August 2018

Comparative study of diesel and biodiesel exhausts on lung oxidative stress and genotoxicity in rats.

Environ Pollut 2018 Apr 8;235:514-524. Epub 2018 Jan 8.

Normandie Univ, UNICAEN, UNIROUEN, ABTE, 14000 Caen et 76000, Rouen, France; Centre François Baclesse, Caen, France. Electronic address:

The contribution of diesel exhaust to atmospheric pollution is a major concern for public health, especially in terms of occurrence of lung cancers. The present study aimed at addressing the toxic effects of a repeated exposure to these emissions in an animal study performed under strictly controlled conditions. Rats were repeatedly exposed to the exhaust of diesel engine. Parameters such as the presence of a particle filter or the use of gasoil containing rapeseed methyl ester were investigated. Various biological parameters were monitored in the lungs to assess the toxic and genotoxic effects of the exposure. First, a transcriptomic analysis showed that some pathways related to DNA repair and cell cycle were affected to a limited extent by diesel but even less by biodiesel. In agreement with occurrence of a limited genotoxic stress in the lungs of diesel-exposed animals, small induction of γ-H2AX and acrolein adducts was observed but not of bulky adducts and 8-oxodGuo. Unexpected results were obtained in the study of the effect of the particle filter. Indeed, exhausts collected downstream of the particle filter led to a slightly higher induction of a series of genes than those collected upstream. This result was in agreement with the formation of acrolein adducts and γH2AX. On the contrary, induction of oxidative stress remained very limited since only SOD was found to be induced and only when rats were exposed to biodiesel exhaust collected upstream of the particle filter. Parameters related to telomeres were identical in all groups. In summary, our results point to a limited accumulation of damage in lungs following repeated exposure to diesel exhausts when modern engines and relevant fuels are used. Yet, a few significant effects are still observed, mostly after the particle filter, suggesting a remaining toxicity associated with the gaseous or nano-particular phases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envpol.2017.12.077DOI Listing
April 2018

Physicochemical characteristics, mutagenicity and genotoxicity of airborne particles under industrial and rural influences in Northern Lebanon.

Environ Sci Pollut Res Int 2017 Aug 15;24(23):18782-18797. Epub 2017 Jun 15.

Unité de Chimie Environnementale et Interactions sur le Vivant, UCEIV, EA 4492, Université du Littoral Côte d'Opale, Dunkerque, France.

In this work, the main objectives were to assess the mutagenic and genotoxic effects of fine particulate matter collected in an industrial influenced site in comparison with a non-industrial influenced one (rural site) and to relate the particulate matter (PM) composition to the observed genotoxic effects. At the industrial influenced site, higher concentrations of phosphates, trace metals, and polycyclic aromatic hydrocarbons (PAHs) in particles could be related to the contributions of quarries, fertilizer producer, cement plants, and tires burning. Gasoline and diesel combustion contributions were evidenced in particles collected at both sites. Particles collected under industrial influence showed a higher mutagenic potential on three tested strains of Salmonella typhimurium (TA98, YG1041, and TA102), and especially on the YG1041, compared to particles from the rural site. Furthermore, only particles collected in the vicinity of the industrial site showed a tendency to activate the SOS responses in Escherichia coli PQ37, which is indicative of DNA damage as a result of exposure of the bacteria cells to the action of mutagenic samples. The mutagenicity and genotoxicity of the industrial PM particulates may be attributed to its composition especially in organic compounds. This study showed that proximity of industries can affect local PM composition as well as PM genotoxic and mutagenic potential.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11356-017-9389-3DOI Listing
August 2017

Smoker extracellular vesicles influence status of human bronchial epithelial cells.

Int J Hyg Environ Health 2017 04 30;220(2 Pt B):445-454. Epub 2016 Dec 30.

Unité de Chimie Environnementale et Interactions sur le Vivant (UCEIV), EA4492, Université du Littoral Côte d'Opale (ULCO), Dunkerque, France. Electronic address:

Cigarette smoking is a habit that has spread all over the world and is a significant risk factor for many diseases including cardiovascular disease, chronic obstructive pulmonary disease (COPD), asthma and lung cancer. Evaluation and understanding of tobacco health effects are of major interest worldwide and answer to important societal concerns. Identification of new biomarkers of exposure to tobacco smoke potentially implicated in COPD or lung carcinogenesis would allow a better observation of tobacco exposed population, thanks to screening establishment at reversible stages of pathological processes. In this study, we questioned whether cigarette smoking alters miRNA profiles of Extracellular Vesicles (EVs) present in human Broncho Alveolar Lavages (BALs), which could affect surrounding normal bronchial epithelial cells status. To this aim, BALs were carried out on 10 Smokers and 10 Non-Smokers, and EVs were isolated from the supernatants and characterized. We then compared the amount of 10 microRNAs (miRNAs) present in Smokers versus Non-Smokers BAL EVs and performed statistical analysis to discuss the biological significance by the smoking status and to evaluate BAL EV miRNAs as potential biomarkers of tobacco exposure. Finally, we tested the effects of smokers versus non-smokers EVs on human bronchial epithelial cells (BEAS-2B) to compare their influence on the cells status. Our study shows for the first time in human samples that smoking can alter lung EV profile that can influence surrounding bronchial epithelial cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijheh.2016.12.010DOI Listing
April 2017

Fine and ultrafine atmospheric particulate matter at a multi-influenced urban site: Physicochemical characterization, mutagenicity and cytotoxicity.

Environ Pollut 2017 Feb 30;221:130-140. Epub 2016 Nov 30.

Univ. Littoral Côte d'Opale, EA 4492 - UCEIV - Unité de Chimie Environnementale et Interactions sur le Vivant, F-59140, Dunkerque, France.

Particulate Matter (PM) air pollution is one of the major concerns for environment and health. Understanding the heterogeneity and complexity of fine and ultrafine PM is a fundamental issue notably for the assessment of PM toxicological effects. The aim of this study was to evaluate mutagenicity and cytotoxicity of a multi-influenced urban site PM, with or without the ultrafine fraction. For this purpose, PM (PM with aerodynamic diameter ranging from 0.3 to 2.5 μm) and PM were collected in Dunkerque, a French coastal industrial city and were extensively characterized for their physico-chemical properties, including inorganic and organic species. In order to identify the possible sources of atmospheric pollution, specific criteria like Carbon Preference Index (CPI) and PAH characteristic ratios were investigated. Mutagenicity assays using Ames test with TA98, TA102 and YG1041 Salmonella strains with or without S9 activation were performed on native PM sample and PM organic extracts and water-soluble fractions. BEAS-2B cell viability and cell proliferation were evaluated measuring lactate dehydrogenase release and mitochondrial dehydrogenase activity after exposure to PM and their extracts. Several contributing sources were identified in PM: soil resuspension, marine emissions including sea-salt or shipping, road traffic and industrial activities, mainly related to steelmaking or petro-chemistry. Mutagenicity of PM was evidenced, especially for PM, including ultrafine fraction, in relation to PAHs content and possibly nitro-aromatics compounds. PM induced cytotoxic effects at relatively high doses, while alteration of proliferation with low PM doses could be related to underlying mechanisms such as genotoxicity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envpol.2016.11.054DOI Listing
February 2017

Usefulness of toxicological validation of VOCs catalytic degradation by air-liquid interface exposure system.

Environ Res 2017 Jan 9;152:328-335. Epub 2016 Nov 9.

Unité de Chimie Environnementale et Interactions sur le Vivant EA4492, Université du Littoral Côte d'Opale, 189A Avenue Maurice Schumann, 59140 Dunkerque, France. Electronic address:

Toluene is one of the most used Volatile Organic Compounds (VOCs) in the industry despite its major health impacts. Catalytic oxidation represents an efficient remediation technique in order to reduce its emission directly at the source, but it can release by-products. To complete the classical performance assessment using dedicated analytical chemistry methods, we propose to perform an untargeted toxicological validation on two efficient catalysts. Using biological system allows integrating synergy and antagonism in toxic effects of emitted VOCs and by-products, often described in case of multi-exposure condition. Catalysts Pd/α-AlO and Pd/γ-AlO developed for the oxidation of toluene were both coupled to a Vitrocell Air-Liquid Interface (ALI) system, for exposure of human A549 lung cells during 1h to toluene or to catalysts exhaust before quantification of xenobiotics metabolizing enzymes. This study validated initially the Vitrocell as an innovative, direct and dynamic model of ALI exposure in the assessment of the performances of new catalysts, showing the presence of chemically undetected by-products. The comparison of the two catalysts showed then that fewer organic compounds metabolizing genes were induced by Pd/γ-AlO in comparison to Pd/α-AlO, suggesting that Pd/γ-AlO is more efficient for toluene total oxidation from a toxicological point of view.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envres.2016.10.027DOI Listing
January 2017

Characterisation and seasonal variations of particles in the atmosphere of rural, urban and industrial areas: Organic compounds.

J Environ Sci (China) 2016 Jun 2;44:45-56. Epub 2016 Mar 2.

Unit of Environmental Chemistry and Interactions with Life, UCEIV-EA4492, Univ. Littoral Côte d'Opale, F-59140 Dunkirk, France.

Atmospheric aerosol samples (PM2.5-0.3, i.e., atmospheric particles ranging from 0.3 to 2.5μm) were collected during two periods: spring-summer 2008 and autumn-winter 2008-2009, using high volume samplers equipped with cascade impactors. Two sites located in the Northern France were compared in this study: a highly industrialised city (Dunkirk) and a rural site (Rubrouck). Physicochemical analysis of particulate matter (PM) was undertaken to propose parameters that could be used to distinguish the various sources and to exhibit seasonal variations but also to provide knowledge of chemical element composition for the interpretation of future toxicological studies. The study showed that PM2.5-0.3 concentration in the atmosphere of the rural area remains stable along the year and was significantly lower than in the urban or industrial ones, for which concentrations increase during winter. High concentrations of polycyclic aromatic hydrocarbons (PAHs), dioxins, furans and dioxin like polychlorinated biphenyls (DL-PCBs), generated by industrial activities, traffic and municipal wastes incineration were detected in the samples. Specific criteria like Carbon Preference Index (CPI) and Combustion PAHs/Total PAHs ratio (CPAHs/TPAHs) were used to identify the possible sources of atmospheric pollution. They revealed that paraffins are mainly emitted by biogenic sources in spring-summer whereas as in the case of PAHs, they have numerous anthropogenic emission sources in autumn-winter (mainly from traffic and domestic heating).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jes.2016.01.014DOI Listing
June 2016

Air Pollution modifies the association between successful and pathological aging throughout the frailty condition.

Ageing Res Rev 2015 Nov 14;24(Pt B):299-303. Epub 2015 Oct 14.

Gérontopôle, Centre Hospitalier Universitaire de Toulouse, Toulouse, France; Inserm UMR1027, Université de Toulouse III Paul Sabatier, Toulouse, France.

The rapid growth in the number of older adults has many implications for public health, including the need to better understand the risks posed by environmental exposures. Aging leads to a decline and deterioration of functional properties at the cellular, tissue and organ level. This loss of functional properties yields to a loss of homeostasis and decreased adaptability to internal and external stress. Frailty is a geriatric syndrome characterized by weakness, weight loss, and low activity that is associated with adverse health outcomes. Frailty manifests as an age-related, biological vulnerability to stressors and decreased physiological reserves. Ambient air pollution exposure affects human health, and elderly people appear to be particularly susceptible to its adverse effects. The aim of this paper is to discuss the role of air pollution in the modulation of several biological mechanisms involved in aging. Evidence is presented on how air pollution can modify the bidirectional association between successful and pathological aging throughout the frailty conditions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.arr.2015.09.004DOI Listing
November 2015

Temporal-spatial variations of the physicochemical characteristics of air pollution Particulate Matter (PM2.5-0.3) and toxicological effects in human bronchial epithelial cells (BEAS-2B).

Environ Res 2015 Feb 16;137:256-67. Epub 2015 Jan 16.

Université Lille Nord de France, Lille, France; EA 4492, Université du Littoral-Côte d'Opale, Dunkerque, France; EA4483, Université de Lille 2, Lille, France. Electronic address:

While the evidence for the health adverse effects of air pollution Particulate Matter (PM) has been growing, there is still uncertainty as to which constituents within PM are most harmful. Hence, to contribute to fulfill this gap of knowledge, some physicochemical characteristics and toxicological endpoints (i.e. cytotoxicity, oxidative damage, cytokine secretion) of PM2.5-0.3 samples produced during two different seasons (i.e. spring/summer or autumn/winter) in three different surroundings (i.e. rural, urban, or industrial) were studied, thereby expecting to differentiate their respective adverse effects in human bronchial epithelial cells (BEAS-2B). Physicochemical characteristics were closely related to respective origins and seasons of the six PM2.5-0.3 samples, highlighting the respective contributions of industrial and heavy motor vehicle traffic sources. Space- and season-dependent differences in cytotoxicity of the six PM2.5-0.3 samples could only be supported by considering both the physicochemical properties and the variance in air PM concentrations. Whatever spaces and seasons, dose- and even time-dependent increases in oxidative damage and cytokine secretion were reported in PM2.5-0.3-exposed BEAS-2B cells. However, the relationship between the chemical composition of each of the six PM2.5-0.3 samples and their oxidative or inflammatory potentials seemed to be very complex. These results supported the role of inorganic, ionic and organic components as exogenous source of Reactive Oxygen Species and, thereafter, cytokine secretion. Nevertheless, one of the most striking observation was that some inorganic, ionic and organic chemical components were preferentially associated with early oxidative events whereas others in the later oxidative damage and/or cytokine secretion. Taken together, these results indicated that PM mass concentration alone might not be able to explain the health outcomes, because PM is chemically nonspecific, and supported growing evidence that PM-size, composition and emission source, together with sampling season, interact in a complex manner to produce PM2.5-0.3-induced human adverse health effects.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envres.2014.12.015DOI Listing
February 2015

Proinflammatory effects and oxidative stress within human bronchial epithelial cells exposed to atmospheric particulate matter (PM(2.5) and PM(>2.5)) collected from Cotonou, Benin.

Environ Pollut 2014 Feb 10;185:340-51. Epub 2013 Dec 10.

Université Lille Nord de France, Lille, France; Unité de Chimie Environnementale et Interactions sur le Vivant (UCEIV) EA 4492, Maison de la Recherche en Environnement Industriel 2, Université du Littoral Côte d'Opale, 189A Avenue Maurice Schumann, 59140 Dunkerque, France.

After particulate matter (PM) collection in Cotonou (Benin), a complete physicochemical characterization of PM2.5 and PM>2.5 was led. Then, their adverse health effects were evaluated by using in vitro culture of human lung cells. BEAS-2B (bronchial epithelial cells) were intoxicated during short-term exposure at increasing PM concentrations (1.5-96 μg/cm(2)) to determine global cytotoxicity. Hence, cells were exposed to 3 and 12 μg/cm(2) to investigate the potential biological imbalance generated by PM toxicity. Our findings showed the ability of both PM to induce oxidative stress and to cause inflammatory cytokines/chemokines gene expression and secretion. Furthermore, PM were able to induce gene expression of enzymes involved in the xenobiotic metabolism pathway. Strong correlations between gene expression of metabolizing enzymes, proinflammatory responses and cell cycle alteration were found, as well as between proinflammatory responses and cell viability. Stress oxidant parameters were highly correlated with expression and protein secretion of inflammatory mediators.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envpol.2013.10.026DOI Listing
February 2014

Xenobiotic metabolism induction and bulky DNA adducts generated by particulate matter pollution in BEAS-2B cell line: geographical and seasonal influence.

J Appl Toxicol 2014 Jun 30;34(6):703-13. Epub 2013 Sep 30.

Université Lille Nord de France, France; ULCO, UCEIV EA4492, F-59140, Dunkerque, France.

Airborne particulate matter (PM) toxicity is of growing interest as diesel exhaust particles have been classified as carcinogenic to humans. However, PM is a mixture of chemicals, and respective contribution of organic and inorganic fractions to PM toxicity remains unclear. Thus, we analysed the link between chemical composition of PM samples and bulky DNA adduct formation supported by CYP1A1 and 1B1 genes induction and catalytic activities. We used six native PM samples, collected in industrial, rural or urban areas, either during the summer or winter, and carried out our experiments on the human bronchial epithelial cell line BEAS-2B. Cell exposure to PM resulted in CYP1A1 and CYP1B1 genes induction. This was followed by an increase in EROD activity, leading to bulky DNA adduct formation in exposed cells. Bulky DNA adduct intensity was associated to global EROD activity, but this activity was poorly correlated with CYPs mRNA levels. However, EROD activity was correlated with both metal and polycyclic aromatic hydrocarbon (PAH) content. Finally, principal components analysis revealed three clusters for PM chemicals, and suggested synergistic effects of metals and PAHs on bulky DNA adduct levels. This study showed the ability of PM samples from various origins to generate bulky DNA adducts in BEAS-2B cells. This formation was promoted by increased expression and activity of CYPs involved in PAHs activation into reactive metabolites. However, our data highlight that bulky DNA adduct formation is only partly explained by PM content in PAHs, and suggest that inorganic compounds, such as iron, may promote bulky DNA adduct formation by supporting CYP activity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jat.2931DOI Listing
June 2014

Prooxidant and proinflammatory potency of air pollution particulate matter (PM₂.₅₋₀.₃) produced in rural, urban, or industrial surroundings in human bronchial epithelial cells (BEAS-2B).

Chem Res Toxicol 2012 Apr 23;25(4):904-19. Epub 2012 Mar 23.

Université Lille Nord de France, Lille, France.

Compelling evidence indicates that exposure to air pollution particulate matter (PM) affects human health. However, how PM composition interacts with PM-size to cause adverse health effects needs elucidation. In this study, we were also interested in the physicochemical characteristics and toxicological end points of PM₂.₅₋₀.₃ samples produced in rural, urban, or industrial surroundings, thereby expecting to differentiate their respective in vitro adverse health effects in human bronchial epithelial cells (BEAS-2B). Physicochemical characteristics of the three PM₂.₅₋₀.₃ samples, notably their inorganic and organic components, were closely related to their respective emission sources. Referring also to the dose/response relationships of the three PM₂.₅₋₀.₃ samples, the most toxicologically relevant exposure times (i.e., 24, 48, and 72 h) and doses (i.e., 3.75 μg PM/cm² and 15 μg PM/cm²) to use to study the underlying mechanisms of action involved in PM-induced lung toxicity were chosen. Organic chemicals adsorbed on the three PM₂.₅₋₀.₃ samples (i.e., polycyclic aromatic hydrocarbons) were able to induce the gene expression of xenobiotic-metabolizing enzymes (i.e., Cytochrome P4501A1 and 1B1, and, to a lesser extent, NADPH-quinone oxidoreductase-1). Moreover, intracellular reactive oxygen species within BEAS-2B cells exposed to the three PM₂.₅₋₀.₃ samples induced oxidative damage (i.e., 8-hydroxy-2'-deoxyguanosine formation, malondialdehyde production and/or glutathione status alteration). There were also statistically significant increases of the gene expression and/or protein secretion of inflammatory mediators (i.e., notably IL-6 and IL-8) in BEAS-2B cells after their exposure to the three PM₂.₅₋₀.₃ samples. Taken together, the present findings indicated that oxidative damage and inflammatory response preceeded cytotoxicity in air pollution PM₂.₅₋₀.₃-exposed BEAS-2B cells and supported the idea that PM-size, composition, and origin could interact in a complex manner to determine the in vitro responsiveness to PM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/tx200529vDOI Listing
April 2012

Benzo[a]pyrene, aflatoxine B₁ and acetaldehyde mutational patterns in TP53 gene using a functional assay: relevance to human cancer aetiology.

PLoS One 2012 3;7(2):e30921. Epub 2012 Feb 3.

Groupe Régional d'Etudes sur le Cancer-EA 1772, Université de Caen Basse-Normandie, Caen, France.

Mutations in the TP53 gene are the most common alterations in human tumours. TP53 mutational patterns have sometimes been linked to carcinogen exposure. In hepatocellular carcinoma, a specific G>T transversion on codon 249 is classically described as a fingerprint of aflatoxin B(1) exposure. Likewise G>T transversions in codons 157 and 158 have been related to tobacco exposure in human lung cancers. However, controversies remain about the interpretation of TP53 mutational pattern in tumours as the fingerprint of genotoxin exposure. By using a functional assay, the Functional Analysis of Separated Alleles in Yeast (FASAY), the present study depicts the mutational pattern of TP53 in normal human fibroblasts after in vitro exposure to well-known carcinogens: benzo[a]pyrene, aflatoxin B(1) and acetaldehyde. These in vitro patterns of mutations were then compared to those found in human tumours by using the IARC database of TP53 mutations. The results show that the TP53 mutational patterns found in human tumours can be only partly ascribed to genotoxin exposure. A complex interplay between the functional impact of the mutations on p53 phenotype and the cancer natural history may affect these patterns. However, our results strongly support that genotoxins exposure plays a major role in the aetiology of the considered cancers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0030921PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3272023PMC
September 2012

Relationship between physicochemical characterization and toxicity of fine particulate matter (PM2.5) collected in Dakar city (Senegal).

Environ Res 2012 Feb 28;113:1-13. Epub 2012 Jan 28.

Université Lille Nord de France, Lille, France.

The massive increase in emissions of air pollutants due to economic and industrial growth in developing countries has made air quality a crucial health problem in this continent. Hence, it is somewhat critical to have a better knowledge on the air pollution in Sub-Saharan Africa countries. Three air pollution PM2.5 samples were also collected in two urban sites (i.e., Fann and Faidherbe) in Dakar (Senegal) and in a rural site near Dakar (i.e., Ngaparu). The two urban sites mainly differ in the type of used vehicles: in Fann, most of the traffic is made of buses, which are absent, in Faidherbe. The physicochemical characteristics of the three PM2.5 samples revealed their high heterogeneities and complexities, related to the multiple natural and anthropogenic emission sources. Results from 5-bromodeoxyuridine incorporation into DNA, mitochondrial dehydrogenase activity, and extracellular lactate dehydrogenase activity in PM2.5-exposed BEAS-2B cells suggested the exposure conditions (i.e., 3 and 12 μg PM/cm² during 24, 48, and 72 h) to further consider. The organic fractions (i.e., mainly PAHs) of the PM(2.5) samples were able to induce a time and/or concentration-dependent gene expression of CYP1A1 and CYP1B1, and, to a lesser extent, NQO1. There was a time and/or dose-dependent increase of both the gene expression and/or protein secretion of inflammatory mediators (i.e., TNF-α, IL-1β, IL-6, and/or IL-8) in PM(2.5)-exposed BEAS-2B cells. In agreement with the physicochemical characterization, urban PM(2.5) samples caused greater biological responses in BEAS-2B cells than the rural one. Variable concentrations of transition metals (i.e., Fe, Al, Pb, Mn, Zn) and organic compounds (i.e., PAHs) founded in the three PM2.5 samples might be firmly involved in a time- and/or dose-dependent toxicity, relying on inflammatory processes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envres.2011.11.009DOI Listing
February 2012

Polycyclic aromatic hydrocarbons within airborne particulate matter (PM(2.5)) produced DNA bulky stable adducts in a human lung cell coculture model.

J Appl Toxicol 2013 Feb 13;33(2):109-19. Epub 2011 Sep 13.

Université Lille Nord de France, Lille, France.

To extend current knowledge on the underlying mechanisms of air pollution particulate matter (PM(2.5))-induced human lung toxicity, the metabolic activation of polycyclic aromatic hydrocarbons (PAH) within PM(2.5) and PAH-DNA bulky stable adduct patterns in human alveolar macrophage (AM) and/or human lung epithelial L132 cells in mono- and cocultures were studied. In the coculture system, only human AM were exposed to air pollution PM(2.5), unlike L132 cells. Particles, inorganic fraction and positive controls [i.e. TiO(2), thermally desorbed PM (dPM) and benzo[a]pyrene, B[a]P, respectively] were included in the experimental design. Cytochrome P450 (CYP) 1A1 gene expression, CYP1A1 catalytic activity and PAH-DNA bulky stable adducts were studied after 24, 48 and/or 72 h. Relatively low doses of PAH within PM(2.5) induced CYP1A1 gene expression and CYP1A1 catalytic activity in human AM and, thereafter, PAH-DNA bulky stable adduct formation. Adduct spots in PM(2.5) -exposed human AM were higher than those in dPM-exposed ones, thereby showing the incomplete removal of PAH by thermal desorption. PAH within air pollution PM(2.5) induced CYP1A1 gene expression but not CYP1A1 catalytic activity in L132 cells. However, despite the absence of PAH-DNA bulky stable adduct in L132 cells from human AM/L132 cell cocultures exposed to dPM(2.5) or PM(2.5), reliable quantifiable PAH-DNA bulky stable adducts were observed in L132 cells from human AM/L132 cell coculture exposed to B[a]P. Taken together, these results support the exertion of genotoxicity of highly reactive B[a]P-derived metabolites produced within human AM not only in primary target human AM, but also in secondary target L132 cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jat.1722DOI Listing
February 2013

Occurrence of molecular abnormalities of cell cycle in L132 cells after in vitro short-term exposure to air pollution PM(2.5).

Chem Biol Interact 2010 Dec 17;188(3):558-65. Epub 2010 Sep 17.

Université Lille Nord de France, Lille, France.

To improve the knowledge of the underlying mechanisms implying in air pollution Particulate Matter (PM)-induced lung toxicity in humans, we were interested in the sequential occurrence of molecular abnormalities from TP53-RB gene signaling pathway activation in the L132 target human lung epithelial cell model. The most toxicologically relevant physical and chemical characteristics of air pollution PM(2.5) collected in Dunkerque, a French highly-industrialized sea-side city, were determined. L132 cells were exposed during 24, 48 and 72h to Dunkerque City's PM(2.5) (i.e. Lethal Concentration (LC)(10)=18.84μgPM/mL or 5.02μgPM/cm(2); LC(50)=75.36μgPM/mL or 20.10μgPM/cm(2)), TiO(2) and desorbed PM (i.e. dPM; EqLC(10)=15.42μg/mL or 4.11μgPM/cm(2); EqLC(50)=61.71μg/mL or 16.46μgPM/cm(2)), benzene (7μM) or Benzo[a]Pyrene (B[a]P; 1μM). Dunkerque City's PM(2.5) altered the gene expression and/or the protein concentration of several key cell cycle controllers from TP53-RB gene signaling pathway (i.e. P53; BCL2; P21; cyclin D1, cyclin-dependent kinase 1; retinoblastoma protein) in L132 cells, thereby leading to the occurrence of cell proliferation and apoptosis together. The activation of the critical cell cycle controllers under study might be related to PM-induced oxidative stress, through the possible involvement of covalent metals in redox systems, the metabolic activation of organic chemicals by enzyme-catalyzed reactions, and phagocytosis. Taken together, these results might ask the critical question whether there is a balance or, in contrast, rather an imbalance between the cell proliferation and the apoptosis occurring in PM-exposed L132 cells, with possible consequences in term of PM-induced lung tumorgenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cbi.2010.09.014DOI Listing
December 2010

Oxidative damage induced in A549 cells by physically and chemically characterized air particulate matter (PM2.5) collected in Abidjan, Côte d'Ivoire.

J Appl Toxicol 2010 May;30(4):310-20

Université Lille Nord de France, Lille, France.

Exposure to high levels of air pollution particulate matter (PM) is strongly associated with increased pulmonary morbidity and mortality. However, the underlying mechanisms of action whereby PM cause adverse health effects are still unclear. In developing countries, like in the sub-Saharian region of Africa, people are often exposed to high PM levels. Hence, three PM(2.5) samples were collected in the District of Abidjan (Côte d'Ivoire), under rural, urban or industrial influences. Their most toxicologically relevant physical and chemical characteristics were determined--thereby showing that most of them were equal or smaller than 2.5 microm--and the influence of both natural (Ca, Na, Mg, Ti, etc.) and anthropic (Al, Fe, Mn, Cr, Pb, Zn, Cu, Ni, benzene and its derivatives, paraffins, etc.) emission sources. The toxicity induced by the three PM samples was studied through 5-bromodeoxyuridine incorporation to DNA, mitochondrial dehydrogenase activity and extracellular lactate dehydrogenase activity. Hence, effect concentrations at 10 and 50% (EC(10) and EC(50), respectively) were as follows: (i) rural PM--EC(10) = 5.91 microg cm(-2) and EC(50) = 29.55 microg cm(-2); (ii) urban PM--EC(10) = 5.45 microg cm(-2) and EC(50) = 27.23 microg cm(-2); and (iii) industrial PM--EC(10) = 6.86 microg cm(-2) and EC(50) = 34.29 microg cm(-2). Moreover, PM-induced oxidative damage in A549 cells was observed through the induction of lipid peroxidation, the alteration of superoxide dismutase activity, and the disruption of glutathione status. Both the transition metals and the organic chemicals within the three collected PM samples under study might be involved in the oxidative damage and, therefore, the toxicity they induced in A549 cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jat.1496DOI Listing
May 2010

Benzene-induced mutational pattern in the tumour suppressor gene TP53 analysed by use of a functional assay, the functional analysis of separated alleles in yeast, in human lung cells.

Arch Toxicol 2010 Feb 28;84(2):99-107. Epub 2009 Oct 28.

LCE EA2598, Toxicologie Industrielle et Environnementale, Université du Littoral-Côte d'Opale, Maison de la Recherche en Environnement Industriel de Dunkerque 2, 189A, Avenue Maurice Schumann, 59140 Dunkerque, France.

Recent concern has centred on the effects of continuous exposure to low concentrations of benzene, both occupationally and environmentally. Although benzene has for a long time been recognised as a carcinogen for humans, its mechanistic pathway remains unclear. Since mutations in the tumour suppressor gene TP53 are the most common genetic alterations involved in human cancer, our objective was to establish the first mutational pattern induced by benzene on the TP53 gene in human type II-like alveolar epithelial A549 cells by using the Functional Analysis of Separated Alleles in Yeast (FASAY). Seventeen mutations linked to benzene exposure were found: 3 one- or two-base deletions, and 14 single nucleotide substitutions (1 nonsense and 13 missense mutations). A>G and G>A transitions were the most prevalent (23.5% for both). Other mutations included A>C transversions and deletions (3/17, 17.6% for both), G>T transversions (2/17, 11.8%) and A>T transversions (1/17, 5.9%). Data arising from this benzene-induced mutational pattern affecting TP53, a critical target gene in human carcinogenesis, have been compared with those reported in human acute myeloid leukaemia, the aetiology of which is clearly linked to benzene exposure, and in experimental benzene-induced carcinoma. This comparison suggests that A>G transition could be a fingerprint of benzene exposure in tumours. Furthermore, our results demonstrate that FASAY is a promising tool for the study of the carcinogenic potency of benzene in the human lung.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00204-009-0478-zDOI Listing
February 2010

Air pollution particulate matter (PM2.5)-induced gene expression of volatile organic compound and/or polycyclic aromatic hydrocarbon-metabolizing enzymes in an in vitro coculture lung model.

Toxicol In Vitro 2009 Feb 8;23(1):37-46. Epub 2008 Oct 8.

LCE-EA2598, Toxicologie Industrielle et Environnementale, MREI 2, Université du Littoral - Côte d'Opale, Maison de la Recherche en Environnement Industriel de Dunkerque 2, 189A, Avenue Maurice Schumann, 59140 Dunkerque, France.

The overarching goals were: (i) to develop an in vitro coculture model, including two relevant lung target cells: human alveolar macrophage (AM) isolated from bronchoalveolar lavage fluid, and immortalized cells originated from the normal lung tissue of a human embryo (L132 cell line), as a future strategy for near-realistic exposures to air pollution particulate matter (PM), and (ii) to study the gene expression of volatile organic compound (VOC) and/or polycyclic aromatic hydrocarbons (PAH)-metabolizing enzymes in this in vitro coculture model. Human AM and/or L132 cells in mono- and coculture were exposed for 24, 48 and 72h to Dunkerque City's PM2.5 at its lethal concentrations at 10% and 50% (i.e. AM: LC10=14.93 microgPM/mL and LC50=74.63 microgPM/mL; L132: LC10=18.84 microgPM/mL and LC50=75.36 microgPM/mL), and the gene expression (i.e. Cytochrome P450 1A1, CYP1A1; CYP2E1; CYP2F1; microsomal Epoxide Hydrolase; NADPH Quinone Oxydo-Reductase-1, NQO1; and Glutathione S-Transferase pi-1 and mu-3, GST-pi1 and GST-mu3) was studied. In human AM in mono- and coculture, and in L132 cells in monoculture, VOC and/or PAH-coated onto PM induced the gene expression of CYP1A1, CYP2E1, NQO1, GST-pi1, and/or GST-mu3. However, there were quiet different outcomes based on the use of L132 cells in mono- vs. coculture: the pattern of VOC and/or PAH-metabolizing enzymes induced by PM in L132 cells in monoculture remained almost unaffected when in coculture with AM. Taken together, these results reinforced the key role of PM-exposed target human AM in the defenses of the human lung from external injuries, notably through their higher capacity to retain PM, and indicated that carbonaceous cores of PM, as physical vector of the penetration and retention of coated-VOC and/or PAH into cells, enabled them to exert a longer toxicity. The use of such a near realistic exposure system could also be a very useful and powerful tool to identify the mechanisms by which air pollution PM induced adverse health effects.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.tiv.2008.09.020DOI Listing
February 2009

Genotoxic potential of Polycyclic Aromatic Hydrocarbons-coated onto airborne Particulate Matter (PM 2.5) in human lung epithelial A549 cells.

Cancer Lett 2008 Oct 12;270(1):144-55. Epub 2008 Jun 12.

LCE EA 2598, Toxicologie Industrielle et Environnementale, Université du Littoral - Côte d'Opale, Maison de la Recherche en Environnement Industriel de Dunkerque 2, 189A, Avenue Maurice Schumann, 59140 Dunkerque, France.

To improve the knowledge of the underlying mechanisms of action involved in air pollution Particulate Matter (PM)-induced toxicity in human lungs, with a particular interest of the crucial role played by coated-organic chemicals, we were interested in the metabolic activation of Polycyclic Aromatic Hydrocarbons (PAH)-coated onto air pollution PM, and, thereafter, the formation of PAH-DNA adducts in a human lung epithelial cell model (A549 cell line). Cells were exposed to Dunkerque city's PM(2.5) at its Lethal Concentrations at 10% and 50% (i.e. LC(10)=23.72 microg/mL or 6.33 microg/cm2, and LC(50)=118.60 microg/mL or 31.63 microg/cm2), and the study of Cytochrome P450 (CYP) 1A1 gene expression (i.e. RT-PCR) and protein activity (i.e. EROD activity), and the formation of PAH-DNA adducts (i.e. 32P-postlabeling), were investigated after 24, 48, and/or 72 h. PAH, PolyChlorinated Dibenzo-p-Dioxins and -Furans (PCDD/F), Dioxin-Like PolyChlorinated Biphenyls (DLPCB), and PolyChlorinated Biphenyls (PCB)-coated onto collected PM were determined (i.e. GC/MS and HRGC/HRMS, respectively), Negative (i.e. TiO2 or desorbed PM, dPM; EqLC10=19.42 microg/mL or 5.18 microg/cm2, and EqLC50=97.13 microg/mL or 25.90 microg/cm2), and positive (i.e. benzo(a)pyrene; 1 microM) controls were included in the experimental design. Statistically significant increases of CYP1A1 gene expression and protein activity were observed in A549 cells, 24, 48 and 72 h after their exposure to dPM, suggesting thereby that the employed outgassing method was not efficient enough to remove total PAH. Both the CYP1A1 gene expression and EROD activity were highly induced 24, 48 and 72 h after cell exposure to PM. However, only very low levels of PAH-DNA adducts, also not reliably quantifiable, were reported 72 h after cell exposure to dPM, and, particularly, PM. The relatively low levels of PAH together with the presence of PCDD/F, DLPCB, and PCB-coated onto Dunkerque City's PM 2.5 could notably contribute to explain the borderline detection of PAH-DNA adducts in dPM and/or PM-exposed A549 cells. Hence, remaining very low doses of PAH in dPM or relatively low doses of PAH-coated onto PM were involved in enzymatic induction, a key feature in PAH-toxicity, but failed to show a clear genotoxicity in this in vitro study. We also concluded that, in the human lung epithelial cell model we used, and in the experimental conditions we chose, bulky-DNA adduct formation was apparently not a major factor involved in the Dunkerque City's PM 2.5-induced toxicity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.canlet.2008.04.044DOI Listing
October 2008

Gene expression induction of volatile organic compound and/or polycyclic aromatic hydrocarbon-metabolizing enzymes in isolated human alveolar macrophages in response to airborne particulate matter (PM2.5).

Toxicology 2008 Feb 29;244(2-3):220-30. Epub 2007 Nov 29.

Service de Pneumologie, Hôpital Saint-Philibert, Groupement Hospitalier de l'Institut Catholique-Faculté Libre de Médecine de Lille, rue du Grand But, BP 249, 59462 Lomme Cedex, France.

To contribute to improve the knowledge of the underlying mechanisms of action involved in air pollution particulate matter (PM)-induced cytotoxicity, we were interested in the metabolic activation of volatile organic compounds (VOC) and/or polycyclic aromatic hydrocarbons (PAH) coated onto Dunkerque City's PM2.5 in human alveolar macrophages (AM) isolated from bronchoalveolar lavage fluid (BALF). This in vitro cell lung model is closer to the normal in vivo situation than other lung cell lines, notably in the characteristics that AM display in terms of gene expression of phase I and phase II-metabolizing enzymes. The bronchoscopic examinations and BAL procedures were carried out without any complications. After 24, 48 and 72h of incubation, calculated lethal concentrations at 10% and 50% of collected airborne PM were 14.93microg PM/mL and 74.63microg PM/mL, respectively, and indicated the higher sensibility of such target lung cells. Moreover, VOC and/or PAH coated onto PM induced gene expression of cytochrome P450 (cyp) 1a1, cyp2e1, nadph quinone oxydo-reductase-1, and glutathione S-transferase-pi 1 and mu 3, versus controls, suggesting thereby the formation of biologically reactive metabolites. In addition, these results suggested the role of physical carrier of carbonaceous core of PM, which can, therefore, increase both the penetration and the retention of attached-VOC into the cells, thereby enabling them to exert a longer induction. Hence, we concluded that the metabolic activation of the very low doses of VOC and/or PAH coated onto Dunkerque City's PM2.5 is one of the underlying mechanisms of action closely involved in its cytotoxicity in isolated human AM in culture.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.tox.2007.11.016DOI Listing
February 2008

Ambient particulate matter (PM2.5): physicochemical characterization and metabolic activation of the organic fraction in human lung epithelial cells (A549).

Environ Res 2007 Oct 25;105(2):212-23. Epub 2007 Apr 25.

LCE EA2598, Toxicologie Industrielle et Environnementale, Université du Littoral-Côte d'Opale, Maison de la Recherche en Environnement Industriel de Dunkerque 2, 189A, Avenue Maurice Schumann, 59140 Dunkerque, France.

To contribute to complete the knowledge of the underlying mechanisms of action involved in air pollution particulate matter (PM)-induced cytotoxicity, an aerosol was collected in Dunkerque, a French seaside City heavily industrialized. In this work, we focused our attention on its physical and chemical characteristics, its cytotoxicity, and its role in the induction of the volatile organic compound (VOC) and/or polycyclic aromatic hydrocarbon (PAH)-metabolizing enzymes in human lung epithelial cells (A549). Size distribution showed that 92.15% of the collected PM were PM2.5 and the specific surface area was 1 m2/g. Inorganic (i.e. Fe, Al, Ca, Na, K, Mg, Pb, etc.) and organic (i.e. VOC, PAH, etc.) chemicals were found in collected PM, revealing that much of them derived from wind-borne dust from the industrial complex and the heavy motor vehicle traffic. The thermal desorption study indicated that organic chemicals were not only adsorbed onto the surface but also highly incrusted in the structure of PM. The lethal concentrations at 10% and 50% of collected PM were 23.72 microg/mL (or 6.33microg/cm2) and 118.60 microg/mL (or 31.63 microg/cm2), respectively. The VOC and/or PAH-coated onto PM induced significant increases in mRNA expressions of cytochrome P450 (cyp) 1a1, cyp2e1, cyp2f1, nadph quinone oxydo-reductase-1, and glutathione s-transferase-pi 1, versus controls. Hence, we concluded that the metabolic activation of the very low doses of VOC and/or PAH-coated onto the inorganic condensation nuclei from Dunkerque City's PM is one of the underlying mechanisms of action closely involved in its cytotoxicity in human lung epithelial cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envres.2007.03.001DOI Listing
October 2007

Role of nuclear factor-kappa B activation in the adverse effects induced by air pollution particulate matter (PM2.5) in human epithelial lung cells (L132) in culture.

J Appl Toxicol 2007 May-Jun;27(3):284-90

LCE EA2598, Toxicologie Industrielle et Environnementale, Maison de la Recherche en Environnement Industriel de Dunkerque 2, 189A, Avenue Maurice Schumann, 59140 Dunkerque, France.

To contribute to improving knowledge on the adverse health effects induced by particulate matter (PM) air pollution, an extensive investigation was undertaken of the underlying mechanisms of action activated by PM(2.5) air pollution collected in Dunkerque, a strongly industrialized French seaside city. Their chemical and physical characteristics have been previously determined, and earlier in vitro short-term studies have shown them to cause dose-dependent and time-dependent oxidative damage, gene expression and protein secretion of inflammatory mediators, and apoptotic events in human lung epithelial cells (L132) in culture. Hence, this work studied the activation of nuclear factor-kappa B (NF-kappaB)/inhibitory kappa B (IkappaB) by Dunkerque city PM(2.5) in these target cells, by determination of phosphorylated p65 and phosphorylated IkappaBalpha protein levels in cytoplasmic extracts, and p65 and p50 DNA binding in nuclear extracts. In PM-exposed L132 cells, there were concentration- and/or time-dependent increases in nuclear p65 and cytoplasmic IkB-alpha phosphorylation, and nuclear p65 and p50 DNA binding. Taken together, these results showed that Dunkerque city PM(2.5) were involved in the activation of the NF-kappaB/IkappaB complex, notably through the occurrence of oxidative stress conditions, and, therefore, in the gene expression and protein secretion of inflammatory mediators in target L132 cells. Hence, these findings suggested that the activation of the NF-kappaB/IkappaB complex preceded cytotoxicity in Dunkerque city PM-exposed L132 cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jat.1211DOI Listing
October 2007