Chemical characterization and in vitro toxicity on human bronchial epithelial cells BEAS-2B of PM2.5_{2.5} from an urban site under industrial emission influence

Particulate Matter (PM) is one of the most relevant environment-related health issues all over the world. In 2013, the International Agency for Research on Cancer (IARC) has classified air pollution and PM as a carcinogen for humans [1]. However, the mechanisms involved in the toxicity of these particles remains poorly understood, mainly because PM are uniquely complex owing to their physicochemical characteristics. In this study, fine particles were collected in the city center of Dunkirk, northern France using a 5 stages high volume cascade impactor (Staplex® 235, 68m3/h) and a Digitel DA80 high volume sampler (30m3/h).Samples were extensively characterized for their physico-chemical properties, including trace metals, water-soluble ions and organic species. Normal human bronchial epithelial cells (BEAS-2B) were used as cell model for toxicological analysis. Cytotoxicity, PAHs-metabolizing enzymes gene expression and genotoxic alterations were evaluated after 24, 48 or 72 h of exposure considering increasing concentrations of PM$_{2.5-0.3}$, organic extracts (OE) and water-soluble fraction (WF) of PM$_{2.5-0.3}$ and PM$_{2.5}$. Several sources such as road traffic, industrial activities mainly related to steelmaking, marine emissions including sea-salts and shipping, as well as soil resuspension were found to contribute to the PM$_{2.5}$ composition. Cytotoxicity assessment results showed time and dose dependent responses, with effects mainly related to PAH compounds in PM$_{2.5}$ OE in which their content were 12 times higher than in PM$_{2.5-0.3}$ one [2]. Differences in the induction of CYP1A1, CYP1B1 and NQO1 genes expression involved in the metabolic activation of organic compounds, as well as genotoxic effects (oxidative DNA adducts, H2A.X phosphorylation) were also evidenced after cells exposure to OE and PM$_{2.5-0.3}$ [3]. These results confirm the major effect of organic compounds on toxic effects, but also the potential contribution of the inorganic fraction of the PM which maintains longer the effects in exposed cells

Atmospheric fine particulate matter and epithelial mesenchymal transition in pulmonary cells: state of the art and critical review of the in vitro studies

International audienceExposure to fine particulate matter (PM2.5) has been associated with several diseases including asthma, chronic obstructive pulmonary disease (COPD) and lung cancer. Mechanisms such as oxidative stress and inflammation are well-documented and are considered as the starting point of some of the pathological responses. However, a number of studies also focused on epithelial-mesenchymal transition (EMT), which is a biological process involved in fibrotic diseases and cancer progression notably via metastasis induction. Up until now, EMT was widely reported in vivo and in vitro in various cell types but investigations dealing with in vitro studies of PM2.5 induced EMT in pulmonary cells are limited. Further, few investigations combined the necessary endpoints for validation of the EMT state in cells: such as expression of several surface, cytoskeleton or extracellular matrix biomarkers and activation of transcription markers and epigenetic factors. Studies explored various cell types, cultured under differing conditions and exposed for various durations to different doses. Such unharmonized protocols (1) might introduce bias, (2) make difficult comparison of results and (3) preclude reaching a definitive conclusion regarding the ability of airborne PM2.5 to induce EMT in pulmonary cells. Some questions remain, in particular the specific PM2.5 components responsible for EMT triggering. The aim of this review is to examine the available PM2.5 induced EMT in vitro studies on pulmonary cells with special emphasis on the critical parameters considered to carry out future research in this field. This clarification appears necessary for production of reliable and comparable results

Les perturbateurs endocriniens : quand ce n’est plus la dose, mais la période d’exposition qui fait le poison

Quelles sont les relations entre les produits toxiques dans notre environnement (COV, glyphosate, bysphénol, nitrites, etc.) et notre santé. Quels sont vrais risques ?De très nombreux produits toxiques sont présents dans notre environnement : dans l’air que nous respirons, dans notre alimentation, dans l’eau que nous buvons, dans les médicaments, etc. Les médias se font régulièrement l’écho de problèmes liés à ces produits toxiques et le grand public se pose de nombreuses questions bien légitimes. Des enseignants-chercheurs, spécialistes en toxicologie répondent de façon simple, compréhensible et sans jargon à un bon nombre de ces questions.Ils abordent simplement les grands concepts :- quelle différence entre le danger et le risque ?- la dose fait-elle le poison ?- qu’est-ce que l’effet cocktail ?- quelle différence entre le principe de prévention et le principe de précaution ?- comment les valeurs réglementaires de concentrations dans les différents milieux sont-elles élaborées ?- quel rôle joue l’environnement sur notre santé depuis notre naissance ?Les auteurs répondent ensuite aux questions posées actuellement par un certain nombre de produits toxiques. Il peut s’agir de pesticides dont on parle beaucoup comme le glyphosate ou le chlordécone, il peut s’agir aussi des contaminants de l’alimentation, de la pollution atmosphérique, des nitrites dans la charcuterie

Inflammation at the Crossroads: the Combined Effects of COVID-19, Ageing, and Air Pollution

International audienceThe global COVID-19 pandemic has highlighted different vulnerability profiles among individuals. With the highest mortality rate, the elderly are a very sensitive group. With regard to the main symptoms, a failure of the respiratory system, associated with deregulation of the immune system, has been observed. These symptoms may also be encountered in chronic exposure of susceptible populations to air pollution, including exacerbation of the inflammatory response. Is there a relationship between age, pollution exposure and the severity of COVID-19? Although it is unclear how these parameters are related, the same pathways can be activated and appear to find a common mechanism of action in inflammation

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

International audienceParticulate 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. PM0.3–2.5 and PM2.5 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 PM2.5 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 PM0.3–2.5, or to the Extractable Organic Matter (EOM) of PM0.3–2.5 and PM2.5. 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 (PM2.5) containing also higher concentrations of polycyclic aromatic hydrocarbons. These results evidenced the major role of organic compounds in the toxicity of PM

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

International audienceBackgroundClassified as carcinogenic to humans by the IARC in 2013, fine air particulate matter (PM2.5) 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.MethodsIn 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 PM2.5.ResultsParticles exposure led to variations in telomerase activity and telomeres length in all age groups without any influence of age. Conversely, P16INK4A gene expression increased significantly with age after exposure to PM2.5. Age could enhance MGMT gene expression after exposure to particles, by decreasing the level of promoter methylation in the oldest people.ConclusionHence, 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

Urban air pollution fine particulate matter exposure: Biomarkers of carcinogenesis modulated by people ageing

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