RESUMEN

Lung cancer is the most common neoplasm and the primary cause-related mortality in developed and in most of nondeveloped countries. Epidemiological studies have demonstrated that even at low arsenic doses, the lungs are one of the main target organs and that chronic arsenic exposure has been associated with an increase in lung cancer development. Among the risk factors for cancer, arsenic methylation efficiency (As3MT) and the clearance of arsenic from cells by two members of the ATP-binding cassette (ABC) transporter family (multidrug resistance protein 1 [MRP1] and P-glycoprotein [P-gp]) play an important role in processing of arsenic and decreasing its intracellular levels. This study aimed to evaluate the association between chronic exposure to arsenic with polymorphism of three proteins involved in arsenic metabolism and efflux of the metalloid in subjects with lung cancer. Polymorphism in As3MT, MRP1, and P-gp modified the arsenic metabolism increasing significantly the AsV urinary levels. A significant association between MRP1 polymorphisms with an increase in the risk for cancer was found. The high inorganic arsenic urinary levels registered in the studied subjects suggest a reduction in the efficiency of As3MT, MRP1, and P-gp firstly because of gene polymorphisms and secondarily because of high internal inorganic arsenic levels. MRP1 polymorphism was associated with a twofold increase in the risk of lung cancer.

Asunto(s)

Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Arsénico/metabolismo , Neoplasias Pulmonares/inducido químicamente , Neoplasias Pulmonares/genética , Metiltransferasas/genética , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/genética , Polimorfismo Genético/genética , Adulto , Anciano , Anciano de 80 o más Años , Arsénico/análisis , Arsénico/orina , Estudios de Cohortes , Estudios Transversales , Agua Potable/análisis , Exposición a Riesgos Ambientales , Femenino , Genotipo , Humanos , Neoplasias Pulmonares/epidemiología , Masculino , Metilación , México/epidemiología , Persona de Mediana Edad , Factores de Riesgo , Encuestas y Cuestionarios , Adulto Joven

RESUMEN

BACKGROUND: Previously we reported that inorganic arsenic (iAs) methylation capacity was associated with breast cancer (BC). BC risk factors may vary according to immunohistochemical subtype. Here we explored the relationships between the capacity to methylate iAs and the risk of BC by subtype. METHODS: A population-based case-control study was performed in northern Mexico. Patients with available information about BC subtypes (n = 499) were age-matched with healthy controls. Sociodemographic, reproductive, and lifestyle characteristics were obtained. Tumor marker information was obtained from medical records. Cases were classified as HR+ [estrogen receptor (ER+) and/or progesterone (PR+), and human epidermal growth factor receptor 2 (HER2-)], HER2+, or triple negative (TN). Urinary arsenic species were determined by high performance liquid chromatography inductively coupled plasma mass spectrometry (HPLC-ICP-MS), and methylation capacity parameters calculated. Conditional logistic regression models were used to estimate BC risk by subtypes. RESULTS: Urinary total arsenic varied from 0.60 to 303.29 µg/L. A significant positive association was found between % monomethylarsonic acid (%MMA) and HR + BC: one percent increase resulted in OR%MMA continuous = 2.73, 95% CI: 1.48, 5.05), and this association remained even when %iAs or % dimethylarsinic acid (%DMA) were added to the models with %MMA. MMA/iAs was positively associated with HR + BC (ORMMA/iAs continuous = 2.03, 95% CI: 1.33-3.10). A significant negative association was observed between DMA/MMA and HR + BC (ORDMA/MMA continuous = 0.43, 95% CI: 0.26, 0.71). MMA/iAs was positively associated with TN BC (OR MMA/iAs continuous = 4.05; 95% CI: 1.63, 10.04). CONCLUSION: Altered iAs methylation capacity resulting in higher %MMA was associated with HR+ and TN BC but not with HER2+. MMA is the iAs metabolite more likely to be related to BC. Further research is needed to confirm these results and elucidate the underlying biological mechanisms.

Asunto(s)

Arsénico , Arsenicales , Neoplasias de la Mama , Arsénico/análisis , Estudios de Casos y Controles , Femenino , Humanos , Metilación , México

RESUMEN

The identification of gene-environment interactions related to breast cancer reveals the biological and molecular mechanisms underlying the disease and allows the distinction of women at high risk from women at lower risk, which could decrease the morbimortality of this neoplasm. The current study evaluated the association between polymorphisms rs1820453 and rs11225161 of the Yes-associated protein (YAP) gene in women with breast cancer exposed to arsenic (As) through drinking water. In total, 182 women were assessed for the frequency of YAP rs1820453 and rs11225161 polymorphisms and As urinary levels. The results demonstrated a positive and significant association between breast cancer and smoking, type of drinking water, and levels of AsIII , AsV and inorganic As (iAs) but not the YAP gene polymorphisms evaluated. In conclusion, our data showed that the source of drinking water and AsV and iAs urinary levels increased the risk for breast cancer, but no interactions between YAP gene polymorphisms and As urinary levels were found.

Asunto(s)

Proteínas Adaptadoras Transductoras de Señales/genética , Arsenicales/efectos adversos , Neoplasias de la Mama/genética , Agua Potable/efectos adversos , Interacción Gen-Ambiente , Polimorfismo de Nucleótido Simple , Factores de Transcripción/genética , Contaminantes Químicos del Agua/efectos adversos , Adulto , Arsenicales/orina , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/etnología , Estudios Transversales , Femenino , Predisposición Genética a la Enfermedad , Humanos , México , Persona de Mediana Edad , Fenotipo , Medición de Riesgo , Factores de Riesgo , Fumar/efectos adversos , Contaminantes Químicos del Agua/orina , Proteínas Señalizadoras YAP

RESUMEN

Environmental arsenic exposure is associated with increased risk of non-cancerous chronic diseases and a variety of cancers in humans. The aims of this study were to carry out for the first time a health risk assessment for two common arsenic exposure routes (drinking water and soil ingestion) in children living in the most important agricultural areas in the Yaqui and Mayo valleys in Sonora, Mexico. Drinking water sampling was conducted in the wells of 57 towns. A cross-sectional study was done in 306 children from 13 villages in the valleys. First morning void urine samples were analyzed for inorganic arsenic (InAs) and monomethyl and dimethyl arsenic (MMA and DMA) by HPLC/ICP-MS. The results showed a wide range of arsenic levels in drinking water between 2.7 and 98.7 µg As/L. Arsenic levels in agricultural and backyard soils were in the range of < 10-27 mg As/kg. The hazard index (HI) = ∑hazard quotient (HQ) for drinking water, agricultural soil, and backyard soil showed values > 1 in 100% of the study towns, and the carcinogenic risk (CR) was greater than 1E-04 in 85%. The average of arsenic excreted in urine was 31.7 µg As/L, and DMA had the highest proportion in urine, with averages of 77.8%, followed by InAs and MMA with 11.4 and 10.9%, respectively, percentages similar to those reported in the literature. Additionally, positive correlations between urinary arsenic levels and HI values were found (r = 0.59, P = 0.000). These results indicated that this population is at high risk of developing chronic diseases including cancer.

Asunto(s)

Arsénico/orina , Agua Potable/química , Exposición a Riesgos Ambientales , Suelo/química , Arsénico/administración & dosificación , Niño , Agua Potable/administración & dosificación , Exposición a Riesgos Ambientales/efectos adversos , Exposición a Riesgos Ambientales/análisis , Femenino , Humanos , Masculino , México , Medición de Riesgo

RESUMEN

Inorganic arsenic (iAs) exposure increases risk of several diseases, including cancer. Some nutrients such as flavonoids enhance glutathione activity, which in turn play a key role in iAs elimination. Our objective was to explore whether dietary non-soy flavonoids are associated with iAs metabolism. We hypothesized that the intake of flavonoids belonging to the following groups, flavan-3-ols, flavone, flavonol, flavanone, and anthocyanidin, is positively associated with urinary dimethylarsinic acid (DMA), which is the most soluble iAs metabolite excreted. We performed a cross-sectional study that included 1027 women living in an arsenic-contaminated area of northern Mexico. Flavonoid intake was estimated using a validated food frequency questionnaire. Concentration of urinary iAs and its metabolites (monomethylarsonic acid and DMA) were determined by high performance liquid chromatography ICP-MS. Results showed positive significant associations between DMA and the flavonoid groups flava-3-ols (ß= 0.0112) and flavones (ß= 0.0144), as well as the individual intake of apigenin (ß= 0.0115), luteolin (ß= 0.0138), and eriodictyol (ß= 0.0026). Our findings suggest that certain non-soy flavonoids may improve iAs elimination; however, there is still very limited information available regarding the consumption of flavonoids and iAs metabolism.

Asunto(s)

Arsénico/farmacocinética , Ácido Cacodílico/orina , Dieta , Flavonoides/farmacología , Extractos Vegetales/farmacología , Contaminantes Químicos del Agua/farmacocinética , Adulto , Anciano , Apigenina/farmacología , Arsénico/orina , Arsenicales/orina , Cromatografía Líquida de Alta Presión , Estudios Transversales , Femenino , Flavanonas/farmacología , Humanos , Luteolina/farmacología , México , Persona de Mediana Edad , Contaminantes Químicos del Agua/orina

RESUMEN

BACKGROUND: Nutrients and genetic polymorphisms participating in one-carbon metabolism may explain interindividual differences in inorganic arsenic (iAs) methylation capacity, which in turn may account for variations in susceptibility to iAs-induced diseases. OBJECTIVES: 1) To evaluate the association between polymorphisms in five one-carbon metabolism genes (FOLH1 c.223 T > C, MTHFD1 c.1958 G > A, MTHFR c.665 C > T, MTR c.2756 A > G, and MTRR c.66 A > G) and iAs methylation capacity; 2) To assess if previously reported associations between nutrient intake and iAs methylation capacity are modified by those polymorphisms. METHODS: Women (n = 1027) exposed to iAs in Northern Mexico were interviewed. Blood and urine samples were collected. Nutrient dietary intake was estimated using a validated food frequency questionnaire. iAs methylation capacity was calculated from urinary iAs species (iAs, monomethylarsonic acid [MMA] and dimethylarsinic acid [DMA]) measured by high performance liquid chromatography (HPLC-ICP-MS). One polymorphism in each of the five genes evaluated was genotyped by allelic discrimination. Multivariable linear regression models were used to evaluate if genetic polymorphisms modified the associations between iAs methylation capacity parameters and nutrient intake. RESULTS: The median (min-max) concentration of total arsenic (TAs) was 20.2 (1.3-2776.0) µg/g creatinine in the study population. Significant interactions for iAs metabolism were only found with FOLH1 c.223 T > C polymorphism and vitamin B12 intake, so that CT and CC genotype carriers had significantly lower %iAs, and higher DMA/iAs with an increased vitamin B12 intake, as compared to carriers of wild-type TT. CONCLUSION: Differences in dietary nutrient intake and genetic variants in one-carbon metabolism may jointly influence iAs methylation capacity. Confirmation of these interactions in other populations is warranted.

Asunto(s)

Arsénico , Polimorfismo Genético , Arsénico/metabolismo , Carbono , Femenino , Humanos , Metilación , Metilenotetrahidrofolato Deshidrogenasa (NADP)/genética , México , Antígenos de Histocompatibilidad Menor/genética , Nutrientes

RESUMEN

UROtsa cells have been accepted as a model to study carcinogenicity mechanisms of arsenic-associated human bladder cancer. In vitro continuous exposure to monomethylarsonous acid (MMAIII), leads UROtsa cells to commit to malignant transformation. In this process, NF-κß-associated inflammatory response seems to play an important role since this transcription factor activates some minutes after cells are exposed in vitro to MMAIII and keeps activated during the cellular malignant transformation. It is known that a slight decrease in the protein phosphatase and tensin homologue (PTEN) gene expression is enough for some cells to become malignantly transformed. Interestingly, this tumor suppressor has been proven to be negatively regulated by NF-κß through binding to its gene promoter. Based on these observations we propose that NF-κß may be involved in arsenic associated carcinogenesis through the negative regulation of PTEN gene expression. Changes in PTEN expression and the binding of p50 NF-κß subunit to PTEN promoter were evaluated in UROtsa cells exposed for 4, 12, 20, or 24 wk to 50nM MMAIII. Results showed that MMAIII induced a significant decrease in PTEN expression around 20 wk exposure to MMAIII,which correlated with increased binding of p50 subunit to the PTEN promoter. Consistent with these results, ChIP assays also showed a significant decrease in H3 acetylation (H3ac) but an increase in the repression marks H3k9me3 and H327me3 in PTEN promoter when compared with not treated cells. These results suggest that the activation of NF-κß by MMAIII may participate in UROtsa cells malignant transformation through the negative regulation of PTEN expression involving p50 homodimers-mediated chromatin remodeling around the PTEN promoter.

Asunto(s)

Histonas/metabolismo , Subunidad p50 de NF-kappa B/metabolismo , Compuestos Organometálicos/toxicidad , Fosfohidrolasa PTEN/metabolismo , Línea Celular , Citocinas/genética , Citocinas/metabolismo , Regulación hacia Abajo , Regulación de la Expresión Génica/fisiología , Histonas/genética , Humanos , Metilación , Subunidad p50 de NF-kappa B/genética , Fosfohidrolasa PTEN/genética , Regiones Promotoras Genéticas

RESUMEN

Community health workers (promotores de salud) have the ability to empower communities to mitigate negative health outcomes. Current training efforts in environmental topics are lacking. This project addressed this gap by developing 4 transferable training modules on environmental health. By applying a series of surveys, interviews, and trainings, we evaluated their relevance. Partners provided favorable feedback for 3 of the 4 modules. It was also learned that the development method could be improved by engaging technically trained promotores de salud in the role of co-creators. This project has implications for environmental justice communities as it can lessen information disparities.

Asunto(s)

Agentes Comunitarios de Salud/organización & administración , Educación en Salud/métodos , Americanos Mexicanos/estadística & datos numéricos , Humanos

RESUMEN

INTRODUCTION: Concentrations of inorganic arsenic (iAs) metabolites in urine present intra- and interindividual variations, which are determined not only by the magnitude of exposure to iAs, but also by differences in genetic, environmental and dietary factors. OBJECTIVE: To evaluate whether differences in dietary intake of selected micronutrients are associated with the metabolism of iAs. METHODS: The intake of 21 micronutrients was estimated for 1027 women living in northern Mexico using a food frequency questionnaire. Concentration of urinary metabolites of iAs was determined by high performance liquid chromatography inductively coupled plasma mass spectrometry (HPLC-ICP-MS) and the proportion of iAs metabolites was calculated (%iAs, monomethylarsonic acid [%MMA] and dimethylarsinic acid [%DMA]), as well as ratios corresponding to the first (MMA/iAs), second (DMA/MMA) and total methylation (DMA/iAs). RESULTS: After adjustment for covariates, it was found that methionine, choline, folate, vitamin B12, Zn, Se and vitamin C favor elimination of iAs mainly by decreasing the %MMA and/or increasing %DMA in urine. CONCLUSIONS: Our results confirm that diet contributes to the efficiency of iAs elimination. Further studies are needed to assess the feasibility of dietary interventions that modulate the metabolism of iAs and the consequent risk of diseases related to its exposure.

Asunto(s)

Arsénico/metabolismo , Micronutrientes/administración & dosificación , Adulto , Anciano , Estudios Transversales , Femenino , Humanos , México , Persona de Mediana Edad

RESUMEN

Disease manifestations or susceptibilities often differ among individuals exposed to the same concentrations of arsenic (As). These differences have been associated with several factors including As metabolism, sex, age, genetic variants, nutritional status, smoking, and others. This study evaluated the associations between four As metabolism-related gene polymorphisms/null genotypes with urinary As methylation profiles in girls and boys chronically exposed to As. In a total of 332 children aged 6-12 years, the frequency of AS3MT, GSTO1, GSTT1, and GSTM1 polymorphisms/null genotypes and As urinary metabolites were measured. The results revealed that total As and monomethyl metabolites of As (MMA) levels were higher in boys than in girls. No differences in the frequency of the evaluated polymorphisms were found between girls and boys. In AS3MT-Met287Thr carriers, %MMA levels were higher and second methylation levels (defined as dimethylarsinic acid divided by MMA) were lower. In children with the GSTM1 null genotype, second methylation levels were higher. In boys, a positive association between the AS3MT-Met287Thr polymorphism with %MMA and between the GSTO1-Glu155del and As(v) was found; whereas, a negative relationship was identified between AS3MT-Met287Thr and second methylation profiles. In girls, a positive association was found between the GSTO1-Ala140Asp polymorphism with second methylation levels. In conclusion, our data indicate that gender, high As exposure levels, and polymorphisms in the evaluated genes negatively influenced As metabolism. Environ. Mol. Mutagen. 57:516-525, 2016. © 2016 Wiley Periodicals, Inc.

Asunto(s)

Arsénico/orina , Glutatión Transferasa/genética , Metiltransferasas/genética , Polimorfismo Genético , Contaminantes Químicos del Agua/orina , Arsénico/metabolismo , Niño , Exposición a Riesgos Ambientales/análisis , Genotipo , Humanos , Metilación , Análisis Multivariante , Factores Sexuales , Factores de Tiempo , Población Urbana , Contaminantes Químicos del Agua/metabolismo

RESUMEN

Long-term exposure to inorganic arsenic (iAs) through drinking water has been associated with cognitive impairment in children and adults; however, the related pathogenic mechanisms have not been completely described. Increased or chronic inflammation in the brain is linked to impaired cognition and neurodegeneration; iAs induces strong inflammatory responses in several cells, but this effect has been poorly evaluated in central nervous system (CNS) cells. Because astrocytes are the most abundant cells in the CNS and play a critical role in brain homeostasis, including regulation of the inflammatory response, any functional impairment in them can be deleterious for the brain. We propose that iAs could induce cognitive impairment through inflammatory response activation in astrocytes. In the present work, rat cortical astrocytes were acutely exposed in vitro to the monomethylated metabolite of iAs (MMAIII), which accumulates in glial cells without compromising cell viability. MMAIII LD50 in astrocytes was 10.52 µM, however, exposure to sub-toxic MMAIII concentrations (50-1000 nM) significantly increased IL-1ß, IL-6, TNF-α, COX-2, and MIF-1 gene expression. These effects were consistent with amyloid precursor protein (APP) and ß-secretase (BACE-1) increased gene expression, mainly for those MMAIII concentrations that also induced TNF-α over-expression. Other effects of MMAIII on cortical astrocytes included increased proliferative and metabolic activity. All tested MMAIII concentrations led to an inhibition of intracellular lactate dehydrogenase (LDH) activity. Results suggest that MMAIII induces important metabolic and functional changes in astrocytes that may affect brain homeostasis and that inflammation may play a major role in cognitive impairment-related pathogenicity in As-exposed populations.

Asunto(s)

Secretasas de la Proteína Precursora del Amiloide/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Ácido Aspártico Endopeptidasas/metabolismo , Astrocitos/efectos de los fármacos , Citocinas/genética , Regulación de la Expresión Génica/efectos de los fármacos , Compuestos Organometálicos/farmacología , Animales , Línea Celular , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Citocinas/metabolismo , Homeostasis/efectos de los fármacos , Ratas Wistar

RESUMEN

The available information concerning metal pollution in different dust sources and the health effects in children remains limited in Mexico. This study focuses on Hermosillo, which is an urbanized area located in the Sonoran Desert in which soil resuspension and dust emission processes are common. The metal content of arsenic (As), chromium (Cr), manganese (Mn), and lead (Pb) were determined in three dust sources (playgrounds, roofs, and roads), each representing different exposure media (EM) for these elements. The metal levels in dust were found in the order of Mn > Cr > Pb > As with the highest metal content found in road dust. Despite the similar average metal distributions, principal component analysis shows a clear separation of the three EM with playground dust related to Cr and Mn and road dust to As and Pb. However, the geoaccumulation index results indicate that dust samples are uncontaminated to moderately polluted, except for Pb in road dust, which is considerably high. In addition, the enrichment factor suggests an anthropogenic origin for all of the studied metals except for Mn. In this context, the hazard index (HI) for noncarcinogenic risk is >1 in this population and thus represents a potential health risk. The spatial distribution for each metal on EM and the HI related to the marginality index could represent a more accurate decision-making tool in risk assessment studies.

Asunto(s)

Polvo/análisis , Exposición a Riesgos Ambientales/análisis , Metales Pesados/análisis , Contaminantes del Suelo/análisis , Exposición a Riesgos Ambientales/estadística & datos numéricos , Humanos , Medición de Riesgo , Urbanización

RESUMEN

The lung is a target organ for adverse health outcomes following exposure to As. Several studies have reported a high prevalence of respiratory symptoms and diseases in subjects highly exposed to As through drinking water; however, most studies to date has been performed in exposed adults, with little information on respiratory effects in children. The objective of the study was to evaluate the association between urinary levels of As and its metabolites with lung function in children exposed in utero and in early childhood to high As levels through drinking water. A total of 358 healthy children were included in our study. Individual exposure was assessed based on urinary concentration of inorganic As. Lung function was assessed by spirometry. Participants were exposed since pregnancy until early childhood to an average water As concentration of 152.13 µg l⁻¹. The mean urinary As level registered in the studied subjects was 141.2 µg l⁻¹ and only 16.7% had a urinary concentration below the national concern level. Forced vital capacity was significantly decreased in the studied population and it was negatively associated with the percentage of inorganic As. More than 57% of the subjects had a restrictive spirometric pattern. The urinary As level was higher in those children with restrictive lung patterns when compared with the levels registered in subjects with normal spirometric patterns. Exposure to As through drinking water during in utero and early life was associated with a decrease in forced vital capacity and with a restrictive spirometric pattern in the children evaluated.

Asunto(s)

Arsénico/toxicidad , Exposición a Riesgos Ambientales/efectos adversos , Enfermedades Ambientales/inducido químicamente , Enfermedades Pulmonares/inducido químicamente , Pulmón/efectos de los fármacos , Efectos Tardíos de la Exposición Prenatal , Contaminantes Químicos del Agua/toxicidad , Arsénico/análisis , Arsénico/orina , Niño , Agua Potable/química , Enfermedades Ambientales/epidemiología , Enfermedades Ambientales/fisiopatología , Enfermedades Ambientales/orina , Monitoreo del Ambiente , Femenino , Humanos , Pulmón/embriología , Pulmón/fisiopatología , Enfermedades Pulmonares/epidemiología , Enfermedades Pulmonares/fisiopatología , Enfermedades Pulmonares/orina , Masculino , México/epidemiología , Embarazo , Prevalencia , Factores de Riesgo , Salud Rural , Índice de Severidad de la Enfermedad , Capacidad Vital/efectos de los fármacos , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/orina , Contaminación Química del Agua/efectos adversos

RESUMEN

Exposure to environmental contaminants, dietary factors and lifestyles may explain worldwide different breast cancer (BC) incidence. Inorganic arsenic (iAs) in the drinking water is a concern in many regions, such as northern Mexico. Studies in several countries have associated the proportion of urinary monomethylarsenic (%MMA) with increased risks for many As-related diseases, including cancer. To investigate the potential relationships between the risk of BC and the capacity to methylate iAs, a hospital-based case-control study (1016 cases/1028 controls) was performed in northern Mexico. Women were directly interviewed about their reproductive histories. The profile of As metabolites in urine was determined by HPLC-ICP-MS and methylation capacity was assessed by metabolite percentages and indexes. Total urinary As, excluding arsenobetaine (TAs-AsB), ranged from 0.26 to 303.29µg/L. Most women (86%) had TAs-AsB levels below As biological exposure index (35µg/L). Women with higher %MMA and/or primary methylation index (PMI) had an increased BC risk (%MMA ORQ5vs.Q1=2.63; 95%CI 1.89,3.66; p for trend <0.001; PMI ORQ5vs.Q1=1.90; 95%CI 1.39,2.59, p for trend <0.001). In contrast, women with higher proportion of urinary dimethylarsenic (%DMA) and/or secondary methylation index (SMI) had a reduced BC risk (%DMA ORQ5vs.Q1=0.63; 95%CI 0.45,0.87, p for trend 0.006; SMI ORQ5vsQ1=0.42, 95%CI 0.31,0.59, p for trend <0.001). Neither %iAs nor total methylation index was associated to BC risk. Inter-individual variations in iAs metabolism may play a role in BC carcinogenesis. Women with higher capacity to methylate iAs to MMA and/or a lower capacity to further methylate MMA to DMA were at higher BC risk.

Asunto(s)

Arsénico/orina , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/orina , Agua Potable/efectos adversos , Contaminantes Químicos del Agua/orina , Neoplasias de la Mama/diagnóstico , Estudios de Casos y Controles , Femenino , Humanos , Metilación , México/epidemiología , Persona de Mediana Edad , Contaminantes Químicos del Agua/efectos adversos

RESUMEN

The incidence of type 2 diabetes mellitus (T2DM) is increasing worldwide and diverse environmental and genetic risk factors are well recognized. Single nucleotide polymorphisms (SNPs) in the calpain-10 gene (CAPN-10), which encodes a protein involved in the secretion and action of insulin, and chronic exposure to inorganic arsenic (iAs) through drinking water have been independently associated with an increase in the risk for T2DM. In the present work we evaluated if CAPN-10 SNPs and iAs exposure jointly contribute to the outcome of T2DM. Insulin secretion (beta-cell function) and insulin sensitivity were evaluated indirectly through validated indexes (HOMA2) in subjects with and without T2DM who have been exposed to a gradient of iAs in their drinking water in northern Mexico. The results were analyzed taking into account the presence of the risk factor SNPs SNP-43 and -44 in CAPN-10. Subjects with T2DM had significantly lower beta-cell function and insulin sensitivity. An inverse association was found between beta-cell function and iAs exposure, the association being more pronounced in subjects with T2DM. Subjects without T2DM who were carriers of the at-risk genotype SNP-43 or -44, also had significantly lower beta-cell function. The association of SNP-43 with beta-cell function was dependent on iAs exposure, age, gender and BMI, whereas the association with SNP-44 was independent of all of these factors. Chronic exposure to iAs seems to be a risk factor for T2DM in humans through the reduction of beta-cell function, with an enhanced effect seen in the presence of the at-risk genotype of SNP-43 in CAPN-10. Carriers of CAPN-10 SNP-44 have also shown reduced beta-cell function.

Asunto(s)

Arsénico/toxicidad , Calpaína/genética , Diabetes Mellitus Tipo 2/patología , Exposición a Riesgos Ambientales/efectos adversos , Células Secretoras de Insulina/citología , Células Secretoras de Insulina/patología , Polimorfismo de Nucleótido Simple , Adulto , Anciano , Diabetes Mellitus Tipo 2/etiología , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/fisiopatología , Contaminantes Ambientales/toxicidad , Femenino , Genotipo , Humanos , Insulina/metabolismo , Resistencia a la Insulina/genética , Secreción de Insulina , Células Secretoras de Insulina/efectos de los fármacos , Células Secretoras de Insulina/metabolismo , Masculino , Persona de Mediana Edad , Proyectos Piloto , Factores de Riesgo

RESUMEN

There is a lack of information of exposure to organochlorine pesticides (OCP) and some metals, such as lead (Pb) and arsenic (As), both of which were used as arsenicals pesticides, in children living in the major agricultural areas of Mexico. The objective of this study was to assess the exposure of children to different OCP, As, and Pb in the Yaqui and Mayo valleys of Sonora to generate population baseline levels of these toxins. A cross-sectional study was undertaken in 165 children (age 6-12 years old) from 10 communities from both valleys during 2009. Blood samples were analyzed for OCP and Pb and first morning void urine for inorganic As (InAs). All of the blood samples had detectable levels of dichlorodiphenyltrichloroethylene (p,p'-DDE) ranging from 0.25 to 10.3 µg/L. However lindane, dichlorodiphenyltrichloroethane (p,p'-DDT), aldrin, and endosulfan were detected in far less of the population (36.4, 23.6, 9.1, and 3 %, respectively). Methoxychlor and endrin were not found in any sample. The average value of Pb in this population was 3.2 µg Pb/dL (range 0.17-9.0) with 8.5 % of the samples having levels <5.0 µg Pb/dL. Urinary As levels ranged from 5.4 to 199 µg As/L with an average value of 31.0 µg As/L. Levels > 50 µg/L were observed in 12.7 % of the samples. Our results show that is important to start a risk-reduction program to decrease exposure to these toxins in Mexican communities. In addition, the results can be used to establish the baseline levels of exposure to these toxins in this agricultural region and may be used as a reference point for regulatory agencies.

Asunto(s)

Agricultura , Arsénico/orina , Exposición a Riesgos Ambientales/análisis , Contaminantes Ambientales , Hidrocarburos Clorados/sangre , Plomo/sangre , Plaguicidas/sangre , Niño , Estudios Transversales , Monitoreo del Ambiente , Contaminantes Ambientales/sangre , Contaminantes Ambientales/orina , Femenino , Humanos , Masculino , México , Población Rural

RESUMEN

Precision-cut liver slices (PCLS) are mainly used to evaluate hepatotoxicity and metabolism of chemicals, as well as to study mechanisms of liver damage and repair. However, recently they have been used as a system to study amoebic infections. The aim of this study was to validate this model as an alternative for experimental amoebic liver absess (ALA) in animals. To do this, the PCLS was analyzed for the expression of amoebapore and cysteine proteinases 1 and 5, three of the most studied virulence factors of Entamoeba histolytica, as well as the induction of apoptosis and cytokines production in response to the ex vivo infection. PCHLS were prepared with the Brendel-Vitron tissue slicer and then, infected with 200,000 trophozoites of E. histolytica. Samples were taken at 0, 6, 12, 18, and 24 h and compared to control non-infected slices. Morphological studies were performed in order to verify the infection; while apoptosis was studied by TUNEL and PAS techniques. The expression of cysteine proteinases (1 and 5), and amoebapore, was analyzed by real-time PCR. By using ELISA assays, the production of cytokines was also studied. PCHLS were found to be a reproducible infection system, and E. histolytica caused the expression of cysteine proteinases and amoebapore in infected slices. At the same time, trophozoites induce release of cytokines and apoptotic death of the hepatocytes close to them. PCHLS represent a new and suitable alternative model to study the pathogenesis of hepatic amoebiasis.

Asunto(s)

Apoptosis , Citocinas/metabolismo , Entamoeba histolytica/patogenicidad , Hígado/parasitología , Factores de Virulencia/metabolismo , Alternativas a las Pruebas en Animales/métodos , Animales , Cricetinae , Proteasas de Cisteína/genética , Proteasas de Cisteína/metabolismo , Modelos Animales de Enfermedad , Entamoeba histolytica/inmunología , Regulación Enzimológica de la Expresión Génica , Etiquetado Corte-Fin in Situ , Hígado/inmunología , Hígado/patología , Masculino , Mesocricetus , Reacción del Ácido Peryódico de Schiff , Reacción en Cadena en Tiempo Real de la Polimerasa , Factores de Virulencia/análisis , Factores de Virulencia/genética

RESUMEN

This investigation examines the extent of soil metal pollution associated with the Green Revolution, relative to agricultural activities and associated risks to health in the most important agricultural region of Mexico. Metal contents in bulk soil samples are commonly used to assess contamination, and metal accumulations in soils are usually assumed to increase with decreasing particle size. This study profiled the spatial distribution of metals (Ni, Cr, Pb, Cu, Fe, Cd, V, Hg, Co, P, Se, and Mn) in bulk soil and fine-grained fractions (soil-derived dust) from 22 towns and cities. The contamination of soil was assessed through the use of a geoaccumulation index (Igeo) and pollution index (PI). The results of this study indicated that a number of towns and cities are moderately to highly polluted by soil containing Be, Co, Hg, P, S, V, Zn, Se, Cr, and Pb in both size fractions (coarse and fine). Hazard index in fine fraction (HI(children)=2.1) shows that risk assessment based on Co, Mn, V, and Ni spatially related to power plants, have the potential to pose health risks to local residents, especially children. This study shows that risk assessment based on metal content in bulk soil could be overestimated when compared to fine-grained fraction. Our results provide important information that could be valuable in establishing risk assessment associated with residential soils within agricultural areas, where children can ingest and inhale dust.

Asunto(s)

Agricultura , Suelo/química , México , Medición de Riesgo

RESUMEN

The association between chronic human exposure to arsenicals and bladder cancer development is well recognized; however, the underlying molecular mechanisms have not been fully determined. We propose that inflammatory responses can play a pathogenic role in arsenic-related bladder carcinogenesis. In previous studies, it was demonstrated that chronic exposure to 50 nM monomethylarsenous acid [MMA(III)] leads to malignant transformation of an immortalized model of urothelial cells (UROtsa), with only 3 mo of exposure necessary to trigger the transformation-related changes. In the three-month window of exposure, the cells over-expressed pro-inflammatory cytokines (IL-1ß, IL-6 and IL-8), consistent with the sustained activation of NFKß and AP1/c-jun, ERK2, and STAT3. IL-8 was over-expressed within hours after exposure to MMA(III), and sustained over-expression was observed during chronic exposure. In this study, we profiled IL-8 expression in UROtsa cells exposed to 50 nM MMA(III) for 1 to 5 mo. IL-8 expression was increased mainly in cells after 3 mo MMA(III) exposure, and its production was also found increased in tumors derived from these cells after heterotransplantation in SCID mice. UROtsa cells do express both receptors, CXCR1 and CXCR2, suggesting that autocrine cell activation could be important in cell transformation. Supporting this observation and consistent with IL-8 over-expression, CXCR1 internalization was significantly increased after three months of exposure to MMA(III). The expression of MMP-9, cyclin D1, bcl-2, and VGEF was significantly increased in cells exposed to MMA(III) for 3 mo, but these mitogen-activated kinases were significantly decreased after IL-8 gene silencing, together with a decrease in cell proliferation rate and in anchorage-independent colony formation. These results suggest a relevant role of IL-8 in MMA(III)-induced UROtsa cell transformation.

Asunto(s)

Transformación Celular Neoplásica/inducido químicamente , Interleucina-8/fisiología , Compuestos Organometálicos/toxicidad , Neoplasias de la Vejiga Urinaria/inducido químicamente , Animales , Proliferación Celular , Células Cultivadas , Humanos , Masculino , Ratones , Ratones SCID , Invasividad Neoplásica , Receptores de Interleucina-8A/análisis , Receptores de Interleucina-8B/análisis , Neoplasias de la Vejiga Urinaria/patología , Urotelio