Browsing by Author "Costa, S."
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- Alterações fenotípicas e genéticas do metabolismo do ferro numa população portuguesa com doença de Alzheimer: potenciais implicações no conhecimento da fisiopatologia e no diagnóstico desta demênciaPublication . Crespo, A.C.; Silva, B.; Marques, L.; Marcelino, E.; Maruta, C.; Costa, S.; Timóteo, A.; Vilares, A.; Couto, F.S.; Faustino, Paula; Correia, A.P.; Verdelho, A.; Porto, G.; Guerreiro, M.; Herrero, A.; Costa, C.; Mendonça, A.; Martins, M.; Costa, L.
- An ECVAG inter-laboratory validation study of the comet assay: inter-laboratory and intra-laboratory variation of DNA strand breaks and FPG-sensitive sites in human mononuclear cellsPublication . Ersson, C.; Møller, P.; Forchhammer, L.; Loft, S.; Azqueta, A.; Godschalk, R.W.; van Schooten, F.J.; Jones, G.D.; Higgins, J.A.; Cooke, M.S.; Mistry, V.; Karbaschi, M.; Phillips, D.H.; Sozeri, O.; Routledge, M.N.; Nelson-Smith, K.; Riso, P.; Porrini, M.; Matullo, G.; Allione, A.; Stepnik, M.; Ferlińska, M.; Teixeira, João Paulo; Costa, S.; Corcuera, L.A.; López de Cerain, A.; Laffon, B.; Valdiglesias, V.; Collins, A.R.; Möller, L.The alkaline comet assay is an established, sensitive method extensively used in biomonitoring studies. This method can be modified to measure a range of different types of DNA damage. However, considerable differences in the protocols used by different research groups affect the inter-laboratory comparisons of results. The aim of this study was to assess the inter-laboratory, intra-laboratory, sample and residual (unexplained) variations in DNA strand breaks and formamidopyrimidine DNA glycosylase (FPG)-sensitive sites measured by the comet assay by using a balanced Latin square design. Fourteen participating laboratories used their own comet assay protocols to measure the level of DNA strand breaks and FPG-sensitive sites in coded samples containing peripheral blood mononuclear cells (PBMC) and the level of DNA strand breaks in coded calibration curve samples (cells exposed to different doses of ionising radiation) on three different days of analysis. Eleven laboratories found dose-response relationships in the coded calibration curve samples on two or three days of analysis, whereas three laboratories had technical problems in their assay. In the coded calibration curve samples, the dose of ionising radiation, inter-laboratory variation, intra-laboratory variation and residual variation contributed to 60.9, 19.4, 0.1 and 19.5%, respectively, of the total variation. In the coded PBMC samples, the inter-laboratory variation explained the largest fraction of the overall variation of DNA strand breaks (79.2%) and the residual variation (19.9%) was much larger than the intra-laboratory (0.3%) and inter-subject (0.5%) variation. The same partitioning of the overall variation of FPG-sensitive sites in the PBMC samples indicated that the inter-laboratory variation was the strongest contributor (56.7%), whereas the residual (42.9%), intra-laboratory (0.2%) and inter-subject (0.3%) variations again contributed less to the overall variation. The results suggest that the variation in DNA damage, measured by comet assay, in PBMC from healthy subjects is assay variation rather than variation between subjects.
- Analysis of cellular damage induced by silica-coated iron oxide nanoparticles on neuronal cellsPublication . Laffon, Blanca; Kiliç, G.; Fernandez Bertólez, N.; Costa, C.; Costa, S.; Teixeira, J.P.; Pásaro, E.; Valdiglesias, V.The objective of this work was to evaluate toxicity induced by silica-coated ION on a human neuronal cell line (SHSY5Y).
- Biomonitoring of several toxic metal(loid)s in different biological matrices from environmentally and occupationally exposed populations from Panasqueira mine area, PortugalPublication . Coelho, P.; Costa, S.; Costa, C.; Silva, S.; Walter, A.; Ranville, J.; Pastorinho, M.R.; Harrington, C.; Taylor, A.; Dall'Armi, V.; Zoffoli, R.; Candeias, C.; da Silva, E.F.; Bonassi, S.; Laffon, B.; Teixeira, João PauloIn the Panasqueira mine area of central Portugal, some environmental media show higher metal(loid) concentrations when compared with the local geochemical background and the values proposed in the literature for these environmental media. In order to evaluate the effect of the external contamination on selected indexes of internal dose, As, Cd, Cu, Cr, Fe, Hg, Mg, Mn, Mo, Ni, Pb, S, Se, Si, and Zn were quantified by inductively coupled plasma mass spectrometry and inductively coupled plasma optical emission spectrometry in blood, urine, hair and nail samples from individuals environmentally (N = 41) and occupationally exposed (N = 41). A matched control group (N = 40) was also studied, and data from the three groups were compared. Results obtained agreed with those reported by environmental studies performed in this area, pointing to populations living nearby and working in the mine being exposed to metal(loid)s originated from mining activities. Arsenic was the element with the highest increase in exposed populations. The concentration of other elements such as Cr, Mg, Mn, Mo, Ni, Pb, S, Se, and Zn was also increased, although at a lesser extent, specifically in the individuals environmentally exposed and in females. These findings confirm the need for competent authorities to act as soon as possible in this area and implement strategies aimed to protect exposed populations and the entire ecosystem.
- A cost-efficiency and health benefit approach to improve urban air qualityPublication . Miranda, A.I.; Ferreira, J.; Silveira, C.; Relvas, H.; Duque, L.; Roebeling, P.; Lopes, M.; Costa, S.; Monteiro, A.; Gama, C.; Sá, E.; Borrego, C.; Teixeira, J.P.When ambient air quality standards established in the EU Directive 2008/50/EC are exceeded, Member States are obliged to develop and implement Air Quality Plans (AQP) to improve air quality and health. Notwithstanding the achievements in emission reductions and air quality improvement, additional efforts need to be undertaken to improve air quality in a sustainable way - i.e. through a cost-efficiency approach. This work was developed in the scope of the recently concluded MAPLIA project "Moving from Air Pollution to Local Integrated Assessment", and focuses on the definition and assessment of emission abatement measures and their associated costs, air quality and health impacts and benefits by means of air quality modelling tools, health impact functions and cost-efficiency analysis. The MAPLIA system was applied to the Grande Porto urban area (Portugal), addressing PM10 and NOx as the most important pollutants in the region. Four different measures to reduce PM10 and NOx emissions were defined and characterized in terms of emissions and implementation costs, and combined into 15 emission scenarios, simulated by the TAPM air quality modelling tool. Air pollutant concentration fields were then used to estimate health benefits in terms of avoided costs (external costs), using dose-response health impact functions. Results revealed that, among the 15 scenarios analysed, the scenario including all 4 measures lead to a total net benefit of 0.3M€·y(-1). The largest net benefit is obtained for the scenario considering the conversion of 50% of open fire places into heat recovery wood stoves. Although the implementation costs of this measure are high, the benefits outweigh the costs. Research outcomes confirm that the MAPLIA system is useful for policy decision support on air quality improvement strategies, and could be applied to other urban areas where AQP need to be implemented and monitored.
- Cytogenetic and immunological effects of formaldehyde in a group of exposed workersPublication . Costa, S.; García-Lestón, J.; Coelho, M.; Coelho, P.; Costa, C.; Silva, S.; Porto, B.; Laffon, B.; Teixeira, João PauloFormaldehyde (FA) is a widely used industrial chemical for which exposure is associated with nasopharyngeal and sinonasal cancer. Based on sufficient evidence of carcinogenicity from human investigations, supporting studies on mechanisms underlying carcinogenesis, and experimental evidence in animals, FA status was recently revised and reclassified as a human carcinogen. The highest level of exposure to FA occurs in occupational settings. Although several studies reported FA ability to induce genotoxic responses in exposed workers, not all findings were conclusive. In addition, published studies on the immunological effects of FA indicate that this compound may be able to modulate immune responses, although data in exposed subjects are still preliminary. In this study a group of pathology anatomy workers exposed to FA was evaluated for cytogenetic and immunological parameters. A control group with similar sociodemographic characteristics and without known occupational exposure to FA was also included. Genotoxicity was evaluated by means of micronucleus (MN) test, sister chromatid exchanges (SCE), and T-cell receptor (TCR) mutation assay. Percentages of different lymphocyte subpopulations were selected as immunotoxic biomarkers. The mean level of FA environmental exposure was 0.36 ± 0.03 ppm. MN and SCE frequencies were significantly increased in the exposed group. A significant decrease of the percentage of B cells in the exposed group was also found. Data obtained in this study indicate that genotoxic and immunotoxic increased risk due to FA occupational exposure cannot be excluded. Implementation of effective control measures along with hazard prevention campaigns may be crucial to decrease the risk.
- Effects of titanium dioxide nanoparticles in human gastric epithelial cells in vitroPublication . Botelho, M.C.; Costa, C.; Silva, S.; Costa, S.; Dhawan, A.; Oliveira, P.A.; Teixeira, João PauloManufacturing or using nanomaterials may result in exposure of workers to nanoparticles. Potential routes of exposure include skin, lung and gastrointestinal tract. The lack of health-based standards for nanomaterials combined with their increasing use in many different workplaces and products emphasize the need for a reliable temporary risk assessment tool. Therefore, the aim of this work was to explore the effects of different doses of titanium dioxide nanoparticles on human gastric epithelial cells in vitro. We analyzed proliferation by MTT assay, apoptosis by Tunel, migration by injury assay, oxidative stress by determining GSH/GSSG ratio and DNA damage by Comet assay on nanoparticle-treated AGS human gastric epithelial cell line in comparison to controls. We show and discuss the tumor-like phenotypes of nanoparticles-exposed AGS cells in vitro, as increased proliferation and decreased apoptosis. Our results demonstrate for the first time that nanoparticles induce tumor-like phenotypes in human gastric epithelial cells.
- Genetic and biochemical markers in patients with Alzheimer's disease support a concerted systemic iron homeostasis dysregulationPublication . Crespo, A.C.; Silva, B.; Marques, L.; Marcelino, E.; Maruta, C.; Costa, S.; Timóteo, A.; Vilares, A.; Couto, F.S.; Faustino, Paula; Correia, A.P.; Verdelho, A.; Porto, G.; Guerreiro, M.; Herrero, A.; Costa, C.; de Mendonça, A.; Costa, L.; Martins, M.Alzheimer's disease (AD) is the most common form of dementia in the elderly individuals, resulting from a complex interaction between environmental and genetic factors. Impaired brain iron homeostasis has been recognized as an important mechanism underlying the pathogenesis of this disease. Nevertheless, the knowledge gathered so far at the systemic level is clearly insufficient. Herein, we used an integrative approach to study iron metabolism in the periphery, at both genotypic and phenotypic levels, in a sample of 116 patients with AD and 89 healthy control subjects. To assess the potential impact of iron metabolism on the risk of developing AD, genetic analyses were performed along with the evaluation of the iron status profile in peripheral blood by biochemical and gene expression studies. The results obtained showed a significant decrease of serum iron, ferritin, and transferrin concentrations in patients compared with the control subjects. Also, a significant decrease of ferroportin (SLC40A1) and both transferrin receptors TFRC and TFR2 transcripts was found in peripheral blood mononuclear cells from patients. At the genetic level, significant associations with AD were found for single nucleotide polymorphisms in TF, TFR2, ACO1, and SLC40A1 genes. Apolipoprotein E gene, a well-known risk factor for AD, was also found significantly associated with the disease in this study. Taken together, we hypothesize that the alterations on systemic iron status observed in patients could reflect an iron homeostasis dysregulation, particularly in cellular iron efflux. The intracellular iron accumulation would lead to a rise in oxidative damage, contributing to AD pathophysiology.
- Geno- and Immunotoxic Effects on Populations Living Near a Mine: A Case Study of Panasqueira Mine in PortugalPublication . Coelho, P.; García-Lestón, J.; Silva, S.; Costa, C.; Costa, S.; Coelho, M.; Laffon, S.; Pásaro Mendez, E.; Teixeira, João PauloMining industry is a vital economic sector for many countries but it is also one of the most hazardous activities, both occupationally and environmentally. Existing studies point to several adverse effects on communities' health living near mines, effects such as mesothelioma and respiratory illnesses. Results achieved in a geochemical sampling campaign undertaken in the vicinity of São Francisco de Assis village showed an anomalous distribution of some heavy metals in soils and waters. To evaluate the effects of mining activities on human health produced by these conditions, a group of 28 individuals from São Francisco de Assis village was examined for some biological endpoints. A nonexposed group (30 individuals) with the same demographic characteristics without exposure to genotoxic compounds was also studied and data obtained from both groups compared. Results of the T-cell receptor mutation assay and micronucleus (MN) test showed significant increases in the frequencies of both mutations and MN in exposed subjects compared to controls. Data obtained in the analysis of the different lymphocyte subsets demonstrated significant decreases in percentages of CD3+ and CD4+ cells, and a significant increase in percentage of CD16/56+ cells, in exposed individuals. The results of the present study indicate an elevated risk of human environmental contamination resulting from mining activities, emphasizing the need to implement preventive measures, remediation, and rehabilitation plans. This would lead to a reduction in cancer risk not only for this particular population but for all populations exposed under similar conditions.
- Genotoxic effect of exposure to metal(loid)s. A molecular epidemiology survey of populations living and working in Panasqueira mine area, PortugalPublication . Coelho, P.; García-Lestón, J.; Costa, S.; Costa, C.; Silva, S.; Dall'Armi, V.; Zoffoli, R.; Bonassi, S.; de Lima, J.P.; Gaspar, J.F.; Pásaro, E.; Laffon, B.; Teixeira, João PauloPrevious studies investigating the exposure to metal(loid)s of populations living in the Panasqueira mine area of central Portugal found a higher internal dose of elements such as arsenic, chromium, lead, manganese, molybdenum and zinc in exposed individuals. The aims of the present study were to evaluate the extent of genotoxic damage caused by environmental and occupational exposure in individuals previously tested for metal(loid) levels in different biological matrices, and the possible modulating role of genetic polymorphisms involved in metabolism and DNA repair. T-cell receptor mutation assay, comet assay, micronucleus (MN) test and chromosomal aberrations (CA) were performed in a group of 122 subjects working in the Panasqueira mine or living in the same region. The modifying effect of polymorphisms in GSTA2, GSTM1, GSTP1, GSTT1, XRCC1, APEX1, MPG, MUTYH, OGG1, PARP1, PARP4, ERCC1, ERCC4, and ERCC5 genes was investigated. Significant increases in the frequency of all biomarkers investigated were found in exposed groups, however those environmentally exposed were generally higher. Significant influences of polymorphisms were observed for GSTM1 deletion and OGG1 rs1052133 on CA frequencies, APEX1 rs1130409 on DNA damage, ERCC1 rs3212986 on DNA damage and CA frequency, and ERCC4 rs1800067 on MN and CA frequencies. Our results show that the metal(loid) contamination in the Panasqueira mine area induced genotoxic damage both in individuals working in the mine or living in the area. The observed effects are closely associated to the internal exposure dose, and are more evident in susceptible genotypes. The urgent intervention of authorities is required to protect exposed populations.
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