Browsing by Author "Laffon, B."
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- 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.
- Biomonitoring of a population of Portuguese workers exposed to leadPublication . García-Lestón, J.; Roma-Torres, J.; Vilares, M.; Pinto, R.; Cunha, L.M.; Prista, J.; Teixeira, João Paulo; Mayan, O.; Pásaro, E.; Méndez, J.; Laffon, B.Lead is a heavy metal that has been used for many centuries and it is still used for various industrial purposes thanks to its physical and chemical characteristics. Human exposure to lead can result in a wide range of biological effects depending upon the level and duration of exposure. Despite the fact that lead has been found capable of eliciting genotoxic responses in a wide range of tests, not all studies have been conclusive. Although several experimental studies have shown that lead may modulate immune responses, data in exposed humans are still preliminary. The purpose of our study was to evaluate the genotoxic and immunotoxic effects of lead exposure in a group of 70 male workers from two Portuguese factories. The control group comprised 38 healthy males. The exposed individuals showed significantly higher levels of lead in blood and zinc protoporphyrin, and significantly lower δ-aminolevulinic acid dehydratase activity than the controls, suggesting a relatively high lead exposure. Nevertheless, the limit of 70 μg/dl for lead in blood established by the Portuguese regulation was never reached. Results of the comet assay were not modified by the exposure, but a significant increase in the mutation frequency in the exposed workers was obtained in the T-cell receptor mutation assay. Furthermore, data obtained in the analysis of the different lymphocyte subsets showed a significant decrease in %CD8+ cells and a significant increase in the %CD4+/%CD8+ ratio in exposed individuals with regard to the controls. No clear effect was observed for vitamin D receptor genetic polymorphism on the parameters evaluated. In view of our results showing mutagenic and immunotoxic effects related to lead exposure in occupational settings, it seems that the Portuguese biological exposure limit for lead needs to be revised in order to increase the safety of exposed workers.
- 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.
- Chemical Exposure and Occupational Symptoms Among Portuguese HairdressersPublication . Mendes, A.; Madureira, J.; Neves, P.; Carvalhais, C.; Laffon, B.; Teixeira, João PauloHairdressing is predominantly a female activity, in which several chemicals are handled, some of which are known to be allergenic and potentially carcinogenic. Several epidemiological studies showed an association between occupational exposure to chemicals in hairdressing salons and skin and respiratory-tract conditions. The aim of this study were to characterize the occupational exposure to total volatile organic compounds (VOC) and ammonia (NH3) in 50 Portuguese hairdressers' salons and to analyze the prevalence of respiratory and skin symptoms in 134 hairdressing professionals. Data indicated that internal sources of total VOC are mainly due to indoor sources, with average concentrations (1.4 mg/m3) above the Portuguese reference levels (0.6 mg/m3). Of the hairdressers' salons studied, 4% had a mean NH3 concentration higher than Portuguese (20 ppm) and American Conference of Industrial Hygienists (ACGIH) (25 ppm) reference levels. Hand dermatitis was the occupational symptom most reported by hairdressers (50%), followed by eye irritation (43%). The results of this study suggest that hairdressers' occupational activities are linked with higher risk of developing hand and wrist/arm dermatitis and symptoms in the upper respiratory tract. The proper use of disposable gloves, hands, wrists, and arms skin monitoring, and the frequent use of moisturizers in the workplace are effective measures to prevent the occurrence of dermatitis in these professionals. Displacement ventilation and/or local exhaust with adequate air exchange rate are recommended particularly in technical areas where hairdressing chemicals are mixed.
- Comparative study on effects of two different types of titanium dioxide nanoparticles on human neuronal cellsPublication . Valdiglesias, V.; Costa, C.; Sharma, V.; Kiliç, G.; Pásaro, E.; Teixeira, João Paulo; Dhawan, A.; Laffon, B.Titanium dioxide (TiO2) are among most frequently used nanoparticles (NPs). They are present in a variety of consumer products, including food industry in which they are employed as an additive. The potential toxic effects of these NPs on mammal cells have been extensively studied. However, studies regarding neurotoxicity and specific effects on neuronal systems are very scarce and, to our knowledge, no studies on human neuronal cells have been reported so far. Therefore, the main objective of this work was to investigate the effects of two types of TiO₂ NPs, with different crystalline structure, on human SHSY5Y neuronal cells. After NPs characterization, a battery of assays was performed to evaluate the viability, cytotoxicity, genotoxicity and oxidative damage in TiO₂ NP-exposed SHSY5Y cells. Results obtained showed that the behaviour of both types of NPs resulted quite comparable. They did not reduce the viability of neuronal cells but were effectively internalized by the cells and induced dose-dependent cell cycle alterations, apoptosis by intrinsic pathway, and genotoxicity not related with double strand break production. Furthermore, all these effects were not associated with oxidative damage production and, consequently, further investigations on the specific mechanisms underlying the effects observed in this study are required.
- 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 iron oxide nanoparticles: Cytotoxicity, genotoxicity, developmental toxicity, and neurotoxicityPublication . Valdiglesias, V.; Kiliç, G.; Costa, C.; Fernández-Bertólez, N; Pásaro, E.; Teixeira, João Paulo; Laffon, B.Iron oxide nanoparticles (ION) with superparamagnetic properties hold great promise for use in various biomedical applications; specific examples include use as contrast agents for magnetic resonance imaging, in targeted drug delivery, and for induced hyperthermia cancer treatments. Increasing potential applications raise concerns over their potential effects on human health. Nevertheless, very little is currently known about the toxicity associated with exposure to these nanoparticles at different levels of biological organization. This article provides an overview of recent studies evaluating ION cytotoxicity, genotoxicity, developmental toxicity and neurotoxicity. Although the results of these studies are sometimes controversial, they generally indicate that surface coatings and particle size seem to be crucial for the observed ION-induced effects, as they are critical determinants of cellular responses and intensity of effects, and influence potential mechanisms of toxicity. The studies also suggest that some ION are safe for certain biomedical applications, while other uses need to be considered more carefully. Overall, the available studies provide insufficient evidence to fully assess the potential risks for human health related to ION exposure. Additional research in this area is required including studies on potential long-term effects.
- 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.
- Genotyping an ALAD polymorphism with real-time PCR in two populations from the Iberian PeninsulaPublication . Moreira, A.O.; Almeida, A.; Costa, S.; Laffon, B.; García-Léston, J.; Pásaro, E.; Méndez, J.; Teixeira, João PauloLead-induced toxicity varies among individuals partly because of genetic differences in their susceptibility to the metal's effects. One genetic polymorphism associated with lead toxicity is a G-to-C transversion at position 177 in the coding region of delta-aminolevulinic acid dehydratase (ALAD), originating from two codominant alleles (ALAD1 and ALAD2). We examined the distribution of this single nucleotide polymorphism in two populations from the Iberian Peninsula. Genomic DNA was extracted from whole blood, and a real-time PCR assay was designed to determine ALAD polymorphic distribution. The distribution of MspI polymorphism was similar in the two populations studied, and allelic frequencies were comparable to those obtained in other studies of Caucasians. Further studies are needed to assess fully the functional significance of this polymorphism and its influence on the toxicokinetics of lead.
- 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.
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