RESUMEN

The heterogeneity and complexity of solvent-extracted organic matter associated with PM2.5 (SEOM-PM2.5) is well known; however, there is scarce information on its biological effects in human cells. This work aimed to evaluate the effect of SEOM-PM2.5 collected in northern Mexico City during the cold-dry season (November 2017) on NL-20 cells, a human bronchial epithelial cell line. The SEOM obtained accounted for 15.5% of the PM2.5 mass and contained 21 polycyclic aromatic hydrocarbons (PAHs). The cell viability decreased following exposure to SEOM-PM2.5, and there were noticeable morphological changes such as increased cell size and the presence of cytoplasmic vesicles in cells treated with 5-40 µg/mL SEOM-PM2.5. Exposure to 5 µg/mL SEOM-PM2.5 led to several alterations compared with the control cells, including the induction of double-stranded DNA breaks based (p < 0.001); nuclear fragmentation and an increased mitotic index (p < 0.05); 53BP1 staining, a marker of DNA repair by non-homologous end-joining (p < 0.001); increased BiP protein expression; and reduced ATF6, IRE1α, and PERK gene expression. Conversely, when exposed to 40 µg/mL SEOM-PM2.5, the cells showed an increase in reactive oxygen species formation (p < 0.001), BiP protein expression (p < 0.05), and PERK gene expression (p < 0.05), indicating endoplasmic reticulum stress. Our data suggest concentration-dependent toxicological effects of SEOM-PM2.5 on NL-20 cells, including genotoxicity, genomic instability, and endoplasmic reticulum stress.

Asunto(s)

Contaminantes Atmosféricos , Bronquios , Supervivencia Celular , Células Epiteliales , Material Particulado , Hidrocarburos Policíclicos Aromáticos , Solventes , Humanos , Células Epiteliales/efectos de los fármacos , Material Particulado/toxicidad , Línea Celular , Contaminantes Atmosféricos/toxicidad , Supervivencia Celular/efectos de los fármacos , Bronquios/citología , Bronquios/efectos de los fármacos , Solventes/toxicidad , Solventes/química , Hidrocarburos Policíclicos Aromáticos/toxicidad , México , Especies Reactivas de Oxígeno/metabolismo

RESUMEN

BACKGROUND: PM2.5 exposure has been associated with intima-media thickness (cIMT) increase. However, very few studies distinguished between left and right cIMT in relation to PM2.5 exposure. AIM: To evaluate associations between chronic exposure to PM2.5 and cIMT at bilateral, left, and right in adults from Mexico City. METHODS: This study comprised 913 participants from the control group, participants without personal or family history of cardiovascular disease, of the Genetics of Atherosclerosis Disease Mexican study (GEA acronym in Spanish), recruited at the Instituto Nacional de Cardiología Ignacio Chávez from June 2008 to January 2013. To assess the associations between chronic exposure to PM2.5 (per 5 µg/m3 increase) at different lag years (1-4 years) and cIMT (bilateral, left, and right) we applied distributed lag non-linear models (DLNMs). RESULTS: The median and interquartile range for cIMT at bilateral, left, and right, were 630 (555, 735), 640 (550, 750), and 620 (530, 720) µm, respectively. Annual average PM2.5 exposure was 26.64 µg/m3, with median and IQR, of 24.46 (23.5-25.46) µg/m3. Results from DLNMs adjusted for age, sex, body mass index, low-density lipoproteins, and glucose, showed that PM2.5 exposure for year 1 and 2, were positively and significantly associated with right-cIMT [6.99% (95% CI: 3.67; 10.42) and 2.98% (0.03; 6.01), respectively]. Negative associations were observed for PM2.5 at year 3 and 4 and right-cIMT; however only year 3 was statistically significant [-2.83% (95% CI: 5.12; -0.50)]. Left-cIMT was not associated with PM2.5 exposure at any lag year. The increase in bilateral cIMT followed a similar pattern as that observed for right-cIMT, but with lower estimates. CONCLUSIONS: Our results suggest different susceptibility between left and right cIMT associated with PM2.5 exposure highlighting the need of measuring both, left and right cIMT, regarding ambient air pollution in epidemiological studies.

Asunto(s)

Contaminación del Aire , Grosor Intima-Media Carotídeo , Exposición a Riesgos Ambientales , Adulto , Humanos , Contaminantes Atmosféricos , Contaminación del Aire/estadística & datos numéricos , Aterosclerosis/epidemiología , Índice de Masa Corporal , Exposición a Riesgos Ambientales/estadística & datos numéricos , México/epidemiología , Material Particulado

RESUMEN

Exposure to fine particulate matter (PM2.5) induces airway inflammation and hyperreactivity that lead to asthma. The mechanisms involved are still under investigation. We investigated the effect of resveratrol (3,4',5-trihydroxystilbene) (RES) on airway hyperresponsiveness, inflammation and CYP1A1 protein expression (an aryl hydrocarbon receptor (AhR) target) induced by PM2.5 exposure in an allergic asthma experimental guinea pig model. The polyphenolic compound RES was used due to its antioxidant and anti-inflammatory properties and as an antagonist of the AhR; thus, providing mechanistic insights. Animals were sensitized with aluminum hydroxide and ovalbumin and exposed to filtered air or PM2.5. Exposure to PM2.5 was conducted using a whole-body chamber particle concentrator (5 h/day) for 15 days. Animals received saline solution or RES (10 mg/kg per day) orally for 21 days simultaneously to the OVA challenge or PM2.5 exposure. PM2.5 exposure (mean 433 ± 111 µg/m3 in the exposure chamber) in OVA challenged animals induced an asthma-like phenotype characterized by increased baseline lung resistance (Rrs) and central airway resistance (Rn) in response to acetylcholine (ACh) evaluated using a flexiVent system®. A parallel increase of pro-inflammatory cytokines (IL-6, IL-17, TNF-α and IFN-γ), inflammatory cells (eosinophils and neutrophils) in bronchoalveolar lavage fluid (BALF) and lung CYP1A1 increase also occurred. RES significantly inhibited airway hyperresponsiveness, inflammation, and CYP1A1 protein expression in the OVA-challenged PM2.5 exposed animals. In summary, with the use of RES we demonstrate that PM-induced airway hyperreactivity is modulated by the inflammatory response via the AhR pathway in an allergic asthma guinea pig model.

Asunto(s)

Asma/inducido químicamente , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/agonistas , Pulmón/efectos de los fármacos , Material Particulado/toxicidad , Neumonía/inducido químicamente , Receptores de Hidrocarburo de Aril/agonistas , Hidróxido de Aluminio , Animales , Antiasmáticos/farmacología , Antiinflamatorios/farmacología , Asma/inmunología , Asma/metabolismo , Asma/prevención & control , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Citocromo P-450 CYP1A1/metabolismo , Citocinas/metabolismo , Modelos Animales de Enfermedad , Cobayas , Mediadores de Inflamación/metabolismo , Pulmón/inmunología , Pulmón/metabolismo , Ovalbúmina , Tamaño de la Partícula , Neumonía/inmunología , Neumonía/metabolismo , Neumonía/prevención & control , Receptores de Hidrocarburo de Aril/metabolismo , Resveratrol/farmacología , Transducción de Señal

RESUMEN

The exposure to environmental pollutants, such as fine and ultrafine particles (FP and UFP), has been associated with increased risk for Parkinson's disease, depression and schizophrenia, disorders related to altered dopaminergic transmission. The striatum, a neuronal nucleus with extensive dopaminergic afferents, is a target site for particle toxicity, which results in oxidative stress, inflammation, astrocyte activation and modifications in dopamine content and D2 receptor (D2R) density. In this study we assessed the in vitro effect of the exposure to FP and UFP on dopaminergic transmission, by evaluating [3H]-dopamine uptake and release by rat striatal isolated nerve terminals (synaptosomes), as well as modifications in the affinity and signaling of native and cloned D2Rs. FP and UFP collected from the air of Mexico City inhibited [3H]-dopamine uptake and increased depolarization-evoked [3H]-dopamine release in striatal synaptosomes. FP and UFP also enhanced D2R affinity for dopamine in membranes from either rat striatum or CHO-K1 cells transfected with the long isoform of the human D2R (hD2LR)2LR). In CHO-K1-hD2L In CHO-K1-hD2LR cells or striatal slices, FP and UFP increased the potency of dopamine or the D2R agonist quinpirole, respectively, to inhibit forskolin-induced cAMP formation. The effects were concentration-dependent, with UFP being more potent than FP. These results indicate that FP and UFP directly affect dopaminergic transmission.

Asunto(s)

Contaminantes Atmosféricos/toxicidad , Cuerpo Estriado/efectos de los fármacos , Dopamina/metabolismo , Material Particulado/toxicidad , Animales , Células CHO , Cuerpo Estriado/metabolismo , Cricetulus , Técnicas In Vitro , Masculino , México , Ratas Wistar , Receptores de Dopamina D2/metabolismo , Transducción de Señal/efectos de los fármacos , Sinaptosomas/efectos de los fármacos , Sinaptosomas/metabolismo

RESUMEN

The physicochemical properties and biological behavior of sintered-bovine-derived hydroxyapatite (BHAp) are here reported and compared to commercial synthetic-HAp (CHAp). Dense ceramics were sintered for 2 h and 4 h at 1200 °C to investigate their microstructure-structure-in-vitro behavior relationship for both HAp ceramics. Densification was directly proportional to sintering time, showing a grain coarsening behavior with a greater effect on BHAp. Lattice parameters, crystallite size, cell volume and Ca/P ratio were determined by Rietveld refinement of X-ray diffraction (XRD) patterns using GSAS®. Ionic substitutions (Na⁺, Mg2+, CO32-) related to BHAp structure were associated with their position changes in the vibrational modes and correlated with the structural parameters obtained from the XRD analysis. Variations in the structural parameters and surface morphology were also evaluated after different soaking periods in simulated body fluid, which is associated with the formation of bone-like apatite layer and thus bioactivity. Mitochondrial activity (MTS) and lactate dehydrogenase (LDH) assays showed that the material released by the ceramics does not induce toxicity after exposure in human fetal osteoblastic (hFOB) cells. Furthermore, no statistically significant differences were found between the HAp obtained from different sources. These results show that BHAp can be used with no restrictions for the same biomedical applications as CHAp.

RESUMEN

Exposure to Particulate Matter (PM) could function as an adjuvant depending on the city of origin in mice allergic asthma models. Therefore, our aim was to determine whether inhalation of fine particles (PM2.5) from Mexico City could act as an adjuvant inducing allergic sensitization and/or worsening the asthmatic response in guinea pig, as a suitable model of human asthma. Experimental groups were Non-Sensitized (NS group), sensitized with Ovalbumin (OVA) plus Aluminum hydroxide (Al(OH)3) as adjuvant (S + Adj group), and sensitized (OVA) without adjuvant (S group). All the animals were exposed to Filtered Air (FA) or concentrated PM2.5 (5 h/daily/3 days), employing an aerosol concentrator system, PM2.5 composition was characterized. Lung function was evaluated by barometric plethysmography (Penh index). Inflammatory cells present in bronchoalveolar lavage were counted as well as OVA-specific IgG1 and IgE were determined by ELISA assay. Our results showed in sensitized animals without Al(OH)3, that the PM2.5 exposure (609 ± 12.73 µg/m3) acted as an adjuvant, triggering OVA-specific IgG1 and IgE concentration. Penh index increased ∼9-fold after OVA challenge in adjuvant-sensitized animals as well as in S + PM2.5 group (∼6-fold), meanwhile NS + FA and S + FA lacked response. S + Adj + PM2.5 group showed an increase significantly of eosinophils and neutrophils in bronchoalveolar lavage. PM2.5 composition was made up of inorganic elements and Polycyclic Aromatic Hydrocarbons, as well as endotoxins and ß-glucan, all these components could act as adjuvant. Our study demonstrated that acute inhalation of PM2.5 acted as an adjuvant, similar to the aluminum hydroxide effect, triggering allergic asthma in a guinea pig model. Furthermore, in sensitized animals with aluminum hydroxide an enhancing influence of PM2.5 exposure was observed as specific-hyperresponsiveness to OVA challenge (quickly response) and eosinophilic and neutrophilic airway inflammation. Fine particles from Mexico City is a complex mix, which play a significant role as adjuvant in allergic asthma.

Asunto(s)

Alérgenos/análisis , Asma , Modelos Animales , Material Particulado/análisis , Aerosoles/análisis , Contaminantes Atmosféricos/análisis , Animales , Líquido del Lavado Bronquioalveolar , Cobayas , Inmunoglobulina E , México , Ratones , Ratones Endogámicos BALB C , Ovalbúmina

RESUMEN

The human glial-cell derived neurotrophic factor (hGDNF) gene transfer by neurotensin (NTS)-polyplex nanoparticles functionally restores the dopamine nigrostriatal system in experimental Parkinson's disease models. However, high levels of sustained expression of GDNF eventually can cause harmful effects. Herein, we report an improved NTS-polyplex nanoparticle system that enables regulation of hGDNF expression within dopaminergic neurons. We constructed NTS-polyplex nanoparticles containing a single bifunctional plasmid that codes for the reverse tetracycline-controlled transactivator advanced (rtTA-Adv) under the control of NBRE3x promoter, and for hGDNF under the control of tetracycline-response element (TRE). Another bifunctional plasmid contained the enhanced green fluorescent protein (GFP) gene. Transient transfection experiments in N1E-115-Nurr1 cells showed that doxycycline (100 ng/mL) activates hGDNF and GFP expression. Doxycycline (5 mg/kg, i.p.) administration in rats activated hGDNF expression only in transfected dopaminergic neurons, whereas doxycycline withdrawal silenced transgene expression. Our results offer a specific doxycycline-regulated system suitable for nanomedicine-based treatment of Parkinson's disease.

Asunto(s)

Neuronas Dopaminérgicas/metabolismo , Doxiciclina/farmacología , Regulación de la Expresión Génica , Nanopartículas/química , Neurotensina/química , Miembro 1 del Grupo A de la Subfamilia 6 de Receptores Nucleares/genética , Animales , Línea Celular Tumoral , Vectores Genéticos , Humanos , Masculino , Ratones , Miembro 1 del Grupo A de la Subfamilia 6 de Receptores Nucleares/metabolismo , Enfermedad de Parkinson/tratamiento farmacológico , Plásmidos , Regiones Promotoras Genéticas , Ratas , Ratas Wistar , Elementos de Respuesta , Transfección , Transgenes

RESUMEN

BACKGROUND: Observed seasonal differences in particulate matter (PM) associations with human health may be due to their composition and to toxicity-related seasonal interactions. OBJECTIVES: We assessed seasonality in PM composition and in vitro PM pro-inflammatory potential using multiple PM samples. METHODS: We collected 90 weekly PM10 and PM2.5 samples during the rainy-warm and dry-cold seasons in five urban areas with different pollution sources. The elements, polycyclic aromatic hydrocarbons (PAHs), and endotoxins identified in the samples were subjected to principal component analysis (PCA). We tested the potential of the PM to induce tumor necrosis factor alpha (TNFα) and interleukin 6 (IL-6) secretion in cultured human monocytes (THP-1), and we modeled pro-inflammatory responses using the component scores. RESULTS: PM composition varied by size and by season. PCA identified two main components that varied by season. Combustion-related constituents (e.g., vanadium, benzo[a]pyrene, benzo[a]anthracene) mainly comprised component 1 (C1). Soil-related constituents (e.g., endotoxins, silicon, aluminum) mainly comprised component 2 (C2). PM from the rainy-warm season was high in C2. PM (particularly PM2.5) from the dry-cold season was rich in C1. Elevated levels of cytokine production were associated with PM10 and C2 (rainy-warm season), whereas reduced levels of cytokine production were associated with PM2.5 and C1 (dry-cold season). TNFα secretion was increased following exposure to PM with high (vs. low) C2 content, but TNFα secretion in response to PM was decreased following exposure to samples containing ≥ 0.1% of C1-related PAHs, regardless of C2 content. The results of the IL-6 assays suggested more complex interactions between PM components and particle size. CONCLUSIONS: Variations in PM soil and PAH content underlie seasonal and PM size-related patterns in TNFα secretion. These results suggest that the mixture of components in PM explains some seasonal differences in associations between health outcomes and PM in epidemiologic studies. CITATION: Manzano-León N, Serrano-Lomelin J, Sánchez BN, Quintana-Belmares R, Vega E, Vázquez-López I, Rojas-Bracho L, López-Villegas MT, Vadillo-Ortega F, De Vizcaya-Ruiz A, Rosas Perez I, O'Neill MS, Osornio-Vargas AR. 2016. TNFα and IL-6 responses to particulate matter in vitro: variation according to PM size, season, and polycyclic aromatic hydrocarbon and soil content. Environ Health Perspect 124:406-412; http://dx.doi.org/10.1289/ehp.1409287.

Asunto(s)

Contaminantes Atmosféricos/toxicidad , Interleucina-6/metabolismo , Material Particulado/toxicidad , Hidrocarburos Policíclicos Aromáticos/toxicidad , Estaciones del Año , Contaminantes del Suelo/toxicidad , Suelo/química , Factor de Necrosis Tumoral alfa/metabolismo , Contaminantes Atmosféricos/química , Línea Celular Tumoral , Ciudades , Endotoxinas/toxicidad , Monitoreo del Ambiente , Humanos , Metales/química , México , Tamaño de la Partícula , Material Particulado/química , Hidrocarburos Policíclicos Aromáticos/química , Contaminantes del Suelo/química

RESUMEN

BACKGROUND: Particulate matter (PM) adverse effects on health include lung and heart damage. The renin-angiotensin-aldosterone (RAAS) and kallikrein-kinin (KKS) endocrine systems are involved in the pathophysiology of cardiovascular diseases and have been found to impact lung diseases. The aim of the present study was to evaluate whether PM exposure regulates elements of RAAS and KKS. METHODS: Sprague-Dawley rats were acutely (3 days) and subchronically (8 weeks) exposed to coarse (CP), fine (FP) or ultrafine (UFP) particulates using a particulate concentrator, and a control group exposed to filtered air (FA). We evaluated the mRNA of the RAAS components At1, At2r and Ace, and of the KKS components B1r, B2r and Klk-1 by RT-PCR in the lungs and heart. The ACE and AT1R protein were evaluated by Western blot, as were HO-1 and γGCSc as indicators of the antioxidant response and IL-6 levels as an inflammation marker. We performed a binding assay to determinate AT1R density in the lung, also the subcellular AT1R distribution in the lungs was evaluated. Finally, we performed a histological analysis of intramyocardial coronary arteries and the expression of markers of heart gene reprogramming (Acta1 and Col3a1). RESULTS: The PM fractions induced the expression of RAAS and KKS elements in the lungs and heart in a time-dependent manner. CP exposure induced Ace mRNA expression and regulated its protein in the lungs. Acute and subchronic exposure to FP and UFP induced the expression of At1r in the lungs and heart. All PM fractions increased the AT1R protein in a size-dependent manner in the lungs and heart after subchronic exposure. The AT1R lung protein showed a time-dependent change in subcellular distribution. In addition, the presence of AT1R in the heart was accompanied by a decrease in HO-1, which was concomitant with the induction of Acta1 and Col3a1 and the increment of IL-6. Moreover, exposure to all PM fractions increased coronary artery wall thickness. CONCLUSION: We demonstrate that exposure to PM induces the expression of RAAS and KKS elements, including AT1R, which was the main target in the lungs and the heart.

Asunto(s)

Sistema Calicreína-Quinina/efectos de los fármacos , Pulmón/efectos de los fármacos , Miocardio/metabolismo , Material Particulado/toxicidad , Sistema Renina-Angiotensina/efectos de los fármacos , Actinas/genética , Actinas/metabolismo , Animales , Antioxidantes/metabolismo , Colágeno Tipo III/genética , Colágeno Tipo III/metabolismo , Citocinas/metabolismo , Regulación de la Expresión Génica , Exposición por Inhalación/efectos adversos , Sistema Calicreína-Quinina/genética , Pulmón/metabolismo , Pulmón/patología , Miocardio/patología , Tamaño de la Partícula , ARN Mensajero/metabolismo , Ratas Sprague-Dawley , Sistema Renina-Angiotensina/genética , Factores de Tiempo

RESUMEN

Particulate matter (PM)-associated metals can contribute to adverse cardiopulmonary effects following exposure to air pollution. The aim of this study was to investigate how variation in the composition and size of ambient PM collected from two distinct regions in Mexico City relates to toxicity differences. Male Wistar Kyoto rats (14 wk) were intratracheally instilled with chemically characterized PM10 and PM2.5 from the north and PM10 from the south of Mexico City (3 mg/kg). Both water-soluble and acid-leachable fractions contained several metals, with levels generally higher in PM10 South. The insoluble and total, but not soluble, fractions of all PM induced pulmonary damage that was indicated by significant increases in neutrophilic inflammation, and several lung injury biomarkers including total protein, albumin, lactate dehydrogenase activity, and γ-glutamyl transferase activity 24 and 72 h postexposure. PM10 North and PM2.5 North also significantly decreased levels of the antioxidant ascorbic acid. Elevation in lung mRNA biomarkers of inflammation (tumor necrosis factor [TNF]-α and macrophage inflammatory protein [MIP]-2), oxidative stress (heme oxygenase [HO]-1, lectin-like oxidized low-density lipoprotein receptor [LOX]-1, and inducibile nitric oxide synthase [iNOS]), and thrombosis (tissue factor [TF] and plasminogen activator inhibitor [PAI]-1), as well as reduced levels of fibrinolytic protein tissue plasminogen activator (tPA), further indicated pulmonary injury following PM exposure. These responses were more pronounced with PM10 South (PM10 South > PM10 North > PM2.5 North), which contained higher levels of redox-active transition metals that may have contributed to specific differences in selected lung gene markers. These findings provide evidence that surface chemistry of the PM core and not the water-soluble fraction played an important role in regulating in vivo pulmonary toxicity responses to Mexico City PM.

Asunto(s)

Contaminantes Atmosféricos/toxicidad , Inflamación/patología , Lesión Pulmonar/patología , Material Particulado/toxicidad , Enfermedad Aguda , Animales , Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/citología , Quimiocina CXCL2/metabolismo , Ciudades , Inflamación/inducido químicamente , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Lesión Pulmonar/inducido químicamente , Masculino , México , Estrés Oxidativo/efectos de los fármacos , Tamaño de la Partícula , Ratas , Ratas Endogámicas WKY , Trombosis/inducido químicamente , Trombosis/patología , Factor de Necrosis Tumoral alfa/metabolismo , Vasoconstricción/efectos de los fármacos

RESUMEN

BACKGROUND: Arsenic exposure is a risk factor for atherosclerosis in adults, but there is little information on arsenic and early risk biomarkers for atherosclerosis in children. Carotid intima-media thickness (cIMT) is an indicator of subclinical atherosclerotic burden that has been associated with plasma asymmetric dimethylarginine (ADMA), a predictor of cardiovascular disease risk. OBJECTIVES: The aim of this study was to investigate associations of arsenic exposure with cIMT, ADMA, and endothelial adhesion molecules [soluble intercellular cell adhesion molecule-1 (sICAM-1); soluble vascular cell adhesion molecule-1 (sVCAM-1)] in children who had been exposed to environmental inorganic arsenic (iAs). METHODS: We conducted a cross-sectional study in 199 children 3-14 years of age who were residents of Zimapan, México. We evaluated cIMT using ultrasonography, and plasma lipid profiles by standard methods. We analyzed ADMA, sICAM-1, and sVCAM-1 by ELISA, and measured the concentrations of total speciated arsenic (tAs) in urine using hydride generation cryotrapping atomic absorption spectrometry. RESULTS: In the multiple linear regression model for cIMT, tAs categories were positively associated with cIMT increase. The estimated cIMT diameter was greater in 35- to 70-ng/mL and > 70-ng/mL groups (0.035 mm and 0.058 mm per 1-ng/mL increase in urinary tAs, respectively), compared with the < 35-ng/mL group. In addition to tAs level, plasma ADMA was a significant predictor of cIMT. In the adjusted regression model, cIMT, percent iAs, and plasma sVCAM-1 were significant predictors of ADMA levels (e.g., 0.419-µmol/L increase in ADMA per 1-mm increase in cIMT). CONCLUSIONS: Arsenic exposure and plasma ADMA levels were positively associated with cIMT in a population of Mexican children with environmental arsenic exposure through drinking water.

Asunto(s)

Arginina/análogos & derivados , Arsénico/toxicidad , Aterosclerosis/epidemiología , Exposición a Riesgos Ambientales/efectos adversos , Túnica Íntima/efectos de los fármacos , Túnica Media/efectos de los fármacos , Adolescente , Arginina/sangre , Aterosclerosis/inducido químicamente , Biomarcadores , Grosor Intima-Media Carotídeo , Niño , Preescolar , Estudios Transversales , Ensayo de Inmunoadsorción Enzimática , Humanos , Modelos Lineales , México/epidemiología , Molécula 1 de Adhesión Celular Vascular/sangre

RESUMEN

Spatial variation in particulate matter-related health and toxicological outcomes is partly due to its composition. We studied spatial variability in particle composition and induced cellular responses in Mexico City to complement an ongoing epidemiologic study. We measured elements, endotoxins, and polycyclic aromatic hydrocarbons in two particle size fractions collected in five sites. We compared the in vitro proinflammatory response of J774A.1 and THP-1 cells after exposure to particles, measuring subsequent TNFα and IL-6 secretion. Particle composition varied by site and size. Particle constituents were subjected to principal component analysis, identifying three components: C(1) (Si, Sr, Mg, Ca, Al, Fe, Mn, endotoxin), C(2) (polycyclic aromatic hydrocarbons), and C(3) (Zn, S, Sb, Ni, Cu, Pb). Induced TNFα levels were higher and more heterogeneous than IL-6 levels. Cytokines produced by both cell lines only correlated with C(1) , suggesting that constituents associated with soil induced the inflammatory response and explain observed spatial differences.

Asunto(s)

Contaminantes Atmosféricos/análisis , Material Particulado/análisis , Material Particulado/toxicidad , Contaminantes Atmosféricos/química , Contaminantes Atmosféricos/toxicidad , Animales , Línea Celular/efectos de los fármacos , Línea Celular/metabolismo , Ciudades , Endotoxinas/análisis , Monitoreo del Ambiente , Humanos , Interleucina-6/metabolismo , México , Ratones , Tamaño de la Partícula , Material Particulado/química , Hidrocarburos Policíclicos Aromáticos/análisis , Análisis de Componente Principal , Pruebas de Toxicidad , Factor de Necrosis Tumoral alfa/metabolismo

RESUMEN

PURPOSE: We aimed to evaluate the association between changes in airborne particulate matter concentration (PM) with changes in cases of mortality, acute respiratory infections (ARI) and asthma over 2004-2008 in an industrialized and polluted region in central Mexico. METHODS: A generalized linear model with a Poisson distribution and a negative binomial analysis was used to evaluate the influence of PM and temperature on all-cause mortality (All-cause-M), cause-specific mortality (Cause-specific-M), ARI and asthma, using cubic spline functions and distributed lags of PM. Estimated changes in relative risk were calculated for an exposure corresponding to each increase of 10 µg/m(3) in PM level. RESULTS: Associations between PM and mortality and morbidity were statistically most consistent for total suspended particulate (TSP) than for particulate matter <10 µM aerodynamic diameter (PM10). The greatest effects in mortality were observed with a 3-week lag, and effects were greater for Cause-specific-M. We also found a displacement effect up to 4-week lag for Cause-specific-M and TSP. The greatest effects in morbidity were observed at 0-week lag, yet they were statistically marginal and were greater for asthma. We found a displacement effect at 4-5-6-week lag for asthma and TSP. All associations of mortality and morbidity, expressed as change in relative risk, were greater with PM10; however, all of them were statistically marginal. CONCLUSIONS: Increased respiratory morbidity and mortality is associated with weekly changes of PM air pollution in the region. A reduction in air pollutants from industrial sources would benefit life quality and health of the exposed population.

Asunto(s)

Asma/inducido químicamente , Asma/mortalidad , Material Particulado/efectos adversos , Infecciones del Sistema Respiratorio/inducido químicamente , Infecciones del Sistema Respiratorio/mortalidad , Temperatura , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisis , Asma/epidemiología , Exposición a Riesgos Ambientales/efectos adversos , Monitoreo del Ambiente , Humanos , México/epidemiología , Reproducibilidad de los Resultados , Infecciones del Sistema Respiratorio/epidemiología

RESUMEN

Arsenic (As) exposure has been associated with alterations in the immune system, studies in experimental models and adults have shown that these effects involve macrophage function; however, limited information is available on what type of effects could be induced in children. The aim of this study was to evaluate effects of As exposure, through the association of inorganic As (iAs) and its metabolites [monomethylated arsenic (MMA) and dimethylated arsenic (DMA)] with basal levels of nitric oxide (NO(-)) and superoxide anion (O(2)(-)), in peripheral blood mononuclear cells (PBMC) and monocytes, and NO(-) and O(2)(-) produced by activated monocytes. Hence, a cross-sectional study was conducted in 87 children (6-10 years old) who had been environmentally exposed to As through drinking water. Levels of urinary As species (iAs, MMA and DMA) were determined by hydride generation atomic absorption spectrometry, total As (tAs) represents the sum of iAs and its species; tAs urine levels ranged from 12.3 to 1411 microg/g creatinine. Using multiple linear regression models, iAs presented a positive and statistical association with basal NO(-) in PBMC (beta=0.0048, p=0.049) and monocytes (beta=0.0044, p=0.044), while basal O(2)(-) had a significant positive association with DMA (beta=0.0025, p=0.046). In activated monocytes, O(2)(-) showed a statistical and positive association with iAs (beta=0.0108, p=0.023), MMA (beta=0.0066, p=0.022), DMA (beta=0.0018, p=0.015), and tAs (beta=0.0013, p=0.015). We conclude that As exposure in the studied children was positively associated with basal levels of NO(-) and O(2)(-) in PBMC and monocytes, suggesting that As induces oxidative stress in circulating blood cells. Additionally, this study showed a positive association of O(2)(-) production with iAs and its metabolites in stimulated monocytes, supporting previous data that suggests that these cells, and particularly the O(2)(-) activation pathway, are relevant targets for As toxicity.

Asunto(s)

Arsénico/toxicidad , Exposición a Riesgos Ambientales/efectos adversos , Leucocitos Mononucleares/efectos de los fármacos , Óxido Nítrico/biosíntesis , Superóxidos/metabolismo , Contaminantes Químicos del Agua/toxicidad , Arsénico/farmacocinética , Niño , Estudios Transversales , Femenino , Humanos , Leucocitos Mononucleares/metabolismo , Masculino , Metilación , Monocitos/efectos de los fármacos , Monocitos/metabolismo , Contaminantes Químicos del Agua/farmacocinética

RESUMEN

Epidemiological evidence has associated exposure to arsenic (As) in drinking water with an increased incidence of human cancers in the skin, bladder, liver, kidney and lung. Sodium arsenite mimics the effects of estradiol and induces cell proliferation in the estrogen responsive breast cancer cell line MCF-7. Therefore, our aim was to further explore the ability of sodium arsenite to induce MCF-7 epithelial breast cell proliferation and some of its underlying mechanisms by studying ROS production, c-Myc and HO-1 protein levels, 8-OHdG formation and NF-kappaB activation. Low arsenite concentrations (0.5-5 microM) induced ROS production and ROS-related depolarization of the mitochondrial membrane suggesting that mitochondria played an important role in the oxidative effects of As. ROS-mediated DNA damage as measured by the presence of 8-OHdG DNA-adducts in their nuclei, IkappaB phosphorylation, NF-kappaB activation and increases in c-Myc and HO-1 protein levels were also observed, suggesting that these factors play a relevant role in the arsenite induced MCF-7 cell recruitment into the S-phase of the cell cycle and cell proliferation observed. In conclusion, arsenite activates several pathways involved in MCF-7 cell proliferation suggesting that arsenite exposure may pose a risk for breast cancer in human exposed populations notwithstanding that most studies to date have not yet implicated this metalloid as a cofactor in the etiology of this disease.

Asunto(s)

Arseniatos/toxicidad , Neoplasias de la Mama/patología , Proliferación Celular/efectos de los fármacos , Daño del ADN , Hemo-Oxigenasa 1/metabolismo , FN-kappa B/metabolismo , Proteínas Proto-Oncogénicas c-myc/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Aductos de ADN/metabolismo , Daño del ADN/fisiología , Evaluación Preclínica de Medicamentos , Humanos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/genética

RESUMEN

Airborne particulate matter (PM) contains a large number of genotoxic substances capable of endangering human health. In the present study, we have investigated the ability of chemically characterized water-soluble and organic-soluble fractions of two particle sizes (PM2.5 and PM10) from different regions of Mexico City to induce DNA damage in a human lung epithelial cell line. We also evaluated associations between the physicochemical parameters of the PM and its genotoxicity. The airborne particulate samples were collected from four regions of the city; a HiVol air sampler was used to collect PM10 on glass fiber filters and a tapered element oscillating system coupled to an automatic cartridge collection unit was used to collect PM2.5 on teflon filters. PM mass was determined by gravimetric analysis of the filters. Filters containing PM2.5 and one section of each PM10 filter were agitated either with deionized water to extract water-soluble compound, or with dichloromethane to prepare organic-soluble compounds. The chemical composition of the extracts was determined by ion and gas chromatography and atomic adsorption spectroscopy. A549 human type II alveolar epithelial cells were exposed to different concentrations of the PM2.5 and PM10 extracts, and alkaline single cell gel electrophoresis or the Comet assay was performed to measure DNA damage and repair. These analyses indicated that soluble transition metals and the organic-soluble PM fractions are crucial factors in the DNA damage induced by PM. PM composition was more important than PM mass for producing genotoxicity. The results of this study showed that the constituents of the water-soluble PM extract are more likely to induce DNA damage than the organic compounds.

Asunto(s)

Contaminantes Atmosféricos , Daño del ADN , Contaminación del Aire , Línea Celular Tumoral , Ciudades , Ensayo Cometa/métodos , Reparación del ADN , Monitoreo del Ambiente , Filtración , Humanos , México , Modelos Estadísticos , Mutágenos , Tamaño de la Partícula , Politetrafluoroetileno , Agua , Tiempo (Meteorología)