Browsing by Author "Coelho, P."
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- Biomarkers, Human HealthPublication . Coelho, P.; Teixeira, João PauloHuman health is constantly affected by a multitude of agents present in the surrounding environment. Biomarkers are key factors, both in clinical health risk assessment and in environmental risk assessment. Traditionally, they are classified in three different classes: exposure, effect, and susceptibility. Their main usefulness relies on their ability to link hazard exposure to the pathogenesis of human disease. The development and validation of biomarkers as early predictors of clinical disease is a top priority, improving health risk assessment and contributing to new disease prevention policies in environmental and occupational settings.
- 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.
- 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.
- 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.
- Immunological alterations in individuals exposed to metal(loid)s in the Panasqueira mining area, Central PortugalPublication . Coelho, P.; García-Lestón, J.; Costa, S.; Costa, C.; Silva, S.; Fuchs, D.; Geisler, S.; Dall'Armi, V.; Zoffoli, R.; Bonassi, S.; Pásaro, E.; Laffon, B.; Teixeira, João PauloEnvironmental studies performed in Panasqueira mine area (central Portugal) identified high concentrations of several metal(loid)s in environmental media, and individuals environmentally and occupationally exposed showed higher levels of As, Cr, Mg, Mn, Mo, Pb and Zn in blood, urine, hair and nails when compared to unexposed controls. To evaluate the presence of immunological alterations attributable to environmental contamination, we quantified neopterin, kynurenine, tryptophan, and nitrite concentrations in plasma, and analysed the percentage of several lymphocytes subsets, namely CD3+, CD4+ and CD8+ T-cells, CD19+ B-cells, and CD16+56+ natural killer (NK) cells in a group of individuals previously tested for metal(loid) levels in different biological matrices. The environmentally exposed group had significantly lower levels of %CD8+ and higher CD4+/CD8+ ratios, whereas the occupationally exposed individuals showed significant decreases in %CD3+ and %CD4+, and significant increases in %CD16+56+, when compared to controls. Analysed biomarkers were found to be influenced by age, particularly neopterin, kynurenine and kynurenine to tryptophan ratio (Kyn/Trp) with significantly higher levels in older individuals, and %CD3+, %CD8+ and %CD19+ with significantly lower values in older individuals. Males environmentally exposed showed significantly lower values of %CD19+ when compared to control females. The concentration of Pb in toenails was associated to the level of neopterin, kynurenine and Kyn/Trp ratio (all direct), and the concentration of Mn in blood to the level of %CD8+, %CD19+ (both inverse) and CD4+/CD8+ ratio (direct). Overall our results show that the metal(loid) contamination in Panasqueira mine area induced immunotoxic effects in exposed populations, possibly increasing susceptibility to diseases.
- Is organic farming safer to farmers' health? A comparison between organic and traditional farmingPublication . Costa, C.; García-Lestón, J.; Costa, S.; Coelho, P.; Silva, S.; Pingarilho, M.; Valdiglesias, V.; Mattei, F.; Dall'Armi, V.; Bonassi, S.; Laffon, B.; Snawder, J.; Teixeira, João PauloExposure to pesticides is a major public health concern, because of the widespread distribution of these compounds and their possible long term effects. Recently, organic farming has been introduced as a consumer and environmental friendly agricultural system, although little is known about the effects on workers' health. The aim of this work was to evaluate genetic damage and immunological alterations in workers of both traditional and organic farming. Eighty-five farmers exposed to several pesticides, thirty-six organic farmers and sixty-one controls took part in the study. Biomarkers of exposure (pyrethroids, organophosphates, carbamates, and thioethers in urine and butyrylcholinesterase activity in plasma), early effect (micronuclei in lymphocytes and reticulocytes, T-cell receptor mutation assay, chromosomal aberrations, comet assay and lymphocytes subpopulations) and susceptibility (genetic polymorphisms related to metabolism - EPHX1, GSTM1, GSTT1 and GSTP1 - and DNA repair-XRCC1 and XRCC2) were evaluated. When compared to controls and organic farmers, pesticide farmers presented a significant increase of micronuclei in lymphocytes (frequency ratio, FR=2.80) and reticulocytes (FR=1.89), chromosomal aberrations (FR=2.19), DNA damage assessed by comet assay (mean ratio, MR=1.71), and a significant decrease in the proportion of B lymphocytes (MR=0.88). Results were not consistent for organic farmers when compared to controls, with a 48% increase of micronuclei in lumphocytes frequency (p=0.016) contrasted by the significant decreases of TCR-Mf (p=0.001) and %T (p=0.001). Our data confirm the increased presence of DNA damage in farmers exposed to pesticides, and show as exposure conditions may influence observed effects. These results must be interpreted with caution due to the small size of the sample and the unbalanced distribution of individuals in the three study groups.
- Micronucleus frequencies in lymphocytes and buccal cells in formaldehyde exposed workersPublication . Costa, S.; Brandão, F.; Coelho, M.; Costa, C.; Coelho, P.; Silva, S.; Porto, B.; Teixeira, João PauloFormaldehyde (FA) is a high-volume production chemical produced worldwide with a large range of industrial and medical uses. Listed, since 2004, by IARC as a human carcinogen, FA status was recently revised by the US government who reclassified this compound as known to be a human carcinogen. Both reclassifications are based on sufficient evidence of carcinogenicity from epidemiologic studies, supporting data on mechanisms of carcinogenesis and experimental evidence in animals. The highest level of human exposure to FA occurs in occupational settings. Consistent findings of increased risks of certain types of rare cancers were found among workers with higher measures of exposure to FA (exposure level or duration). The aim of the present study was to assess the genotoxic effects of occupational exposure to FA. A group of pathology and anatomy workers was evaluated for micronuclei in lymphocytes and in exfoliated buccal cells. Genotoxic endpoints are of great interest in the risk assessment of occupational carcinogens because they precede by a long time the potential health effects, thus offering a greater potential for preventive measures. Micronuclei in lymphocytes and in exfoliated buccal cells were significantly higher in the exposed subjects when compared with controls. Air sampling was performed in the workers’ breathing zone for representative working periods and an 8h-time weighted average was assessed.
- Micronucleus Frequencies in Lymphocytes and Reticulocytes in a Pesticide-Exposed Population in PortugalPublication . Costa, C.; Silva, S.; Neves, J.; Coelho, P.; Costa, S.; Laffon, B.; Snawder, J.; Teixeira, João PauloA wide range of chemical products known to be acutely toxic is currently used in the agricultural sector, including numerous pesticides with different compositions. Nevertheless, the effects in human health as result of chronic exposure to low levels are not yet completely understood. The methodology for determination of micronuclei (MN) in lymphocytes (CBMN) is well established, and accumulating data demonstrated a correlation to enhanced risk of cancer development. However, analysis of MN in reticulocytes (MN-RET) in humans is a recent tool on human biomonitoring. The aim of this study was to examine the influence of pesticide exposure on MN-RET and CBMN frequencies. In total, 177 individuals were studied (93 controls and 84 exposed). All individuals included in the exposed group were exposed regularly to various chemicals. Both MN-RET and CBMN were significantly higher in the exposed subjects compared to controls. The CBMN frequencies were quantitatively higher in females than males, especially within the exposed group. Smoking habits exerted no marked influence on the frequency of the biomarkers studied. A significant and positive correlation was found between both indicators. Within the exposed group, data showed that there was a significant correlation between MN-RET and recent exposure (exposure in the previous 10 d) that is not found when considering CBMN. It is conceivable that due to the short life span of reticulocytes, MN-RET were found to be more reliable to characterize recent genetic damage as opposed to CBMN.
- Multiple genotoxic activities of ptaquiloside in human lymphocytes: aneugenesis, clastogenesis and induction of sister chromatid exchangePublication . Gil da Costa, R.M.; Coelho, P.; Sousa, R.; Bastos, M.M.S.M.; Porto, B.; Teixeira, João Paulo; Malheiro, I; Lopes, C.Ptaquiloside, a norsesquiterpene glycoside from bracken (Pteridium aquilinum), is a known carcinogen towards animals. Its genotoxicity is mainly attributed to its DNA-alkylating and clastogenic properties. This study analyses various modes of genotoxic action of ptaquiloside in human mononuclear blood cells. The alkaline comet assay was performed on cells exposed to 5μg/ml ptaquiloside for 5, 10, 20, 30, 40 or 50min. Tail length was used as a DNA-damage parameter. Assays to determine structural and numerical chromosomal aberrations and sister-chromatid exchange were conducted on cells exposed to 5, 10 or 20μg/ml ptaquiloside for 48h. The tail length showed maximum DNA damage at 20-30min, diminishing onwards. Highly significant (p<0.001) dose-dependent increases in structural and numerical chromosomal aberrations and SCE were observed in response to ptaquiloside. These results indicate that ptaquiloside is not only a DNA-alkylating agent, but expresses its genotoxicity through multiple mechanisms including clastogenesis, aneugenesis and the mechanism underlying SCE induction, which is not entirely understood. Recent studies support the role played by aneuploidy in oncogenesis, highlighting the importance of this endpoint for mutagenicity screening. SCE are thought to represent the long-term effects of mutagens and are an important genotoxicity biomarker. The present results also agree with data from epidemiological studies and from animal in vivo studies, further supporting the hypothesis that ptaquiloside may represent a significant threat to human health.