Loading...
155 results
Search Results
Now showing 1 - 10 of 155
- Micronutrients intake associated with DNA damage assessed by in a human biomonitoring studyPublication . Ladeira, Carina; Viegas, Susana; Carolino, Elisabete; Gomes, Manuel C.; Brito, MiguelNutrition science has evolved into a multidisciplinary field that applies molecular biology and integrates individual health with the epidemiologic investigation of population health. Nutritional genomics studies the functional interaction of food and its components, macro and micronutrients, with the genome at the molecular, cellular, and systemic level. Diet can influence cancer development in several ways, namely direct action of carcinogens in food that can damage DNA, diet components (macro or micronutrients) that can block or induce enzymes involved in activation or deactivation of carcinogenic substances. Moreover, inadequate intake of some molecules involved in DNA synthesis, repair or methylation can influence mutation rate or changes in gene expression. Several studies support the idea that diet can influence the risk of cancer; however information concerning the precise dietary factor that determines human cancer is an ongoing debate. A lot of epidemiological studies, involving food frequency questionnaires, have been developed providing important information concerning diet and cancer, however, diet is a complex composite of various nutrients (macro and micronutrients) and non-nutritive food constituents that makes the search for specific factors almost limitless.
- Genotoxicity biomarkers micronucleus, nucleoplasmic bridges and nuclear budsPublication . Ladeira, CarinaThe increase of mortality from cancer brought urgency in identification and validation of predictive markers of risk and therefore early diagnosis. There is evidence that cytogenetic biomarkers are positively correlated with risk of cancer, and this is validated by studies of cohort and case-control. Cytokinesis-blocked micronucleus (CBMN) assay is used extensively in molecular epidemiology, and can be considered as a “cytome” assay covering cell proliferation, apoptosis, necrosis and chromosomal changes. The chromosomal alterations most reported and studied by the CBMN are: micronucleus (MN), nucleoplasmic bridges (NPB) and nuclear buds (NBUDS). The use of the MN assay in biomonitoring studies had a large increase in the last 15 years and international projects such as the HUMN have helped to increase the applicability and reliability of these tests.
- Cytostatics occupational exposure: genotoxic effects assessmentPublication . Ladeira, Carina; Viegas, Susana; Carolino, Elisabete; Gomes, M. C.; Brito, MiguelThe use of cytostatics drugs in anticancer therapy is increasing. Health care workers can be occupationally exposed to these drugs classified as carcinogenic, mutagenic or teratogenic. Workers may be exposed to this drug, being in the hospital settings the main focus dwelled upon the pharmacy, and nursing personnel. Although the potential therapeutic benefits of hazardous drugs outweigh the risks of side effects for ill patients, exposed health care workers can have the same side effects with no therapeutic benefit. The exposure to these substances is epidemiologically linked to cancer and nuclear changes detected by the cytokinesis-block micronucleus test (CBMN). This method is extensively used in molecular epidemiology, since it determines several biomarkers of genotoxicity, such as micronuclei (MN), which are biomarkers of chromosomes breakage or loss, nucleoplasmic bridges (NPB), common biomarkers of chromosome rearrangement, poor repair and/or telomeres fusion, and nuclear buds (NBUD), biomarkers of elimination of amplified DNA.
- Role of macronutrients and micronutrients in DNA damage: results from a food frequency questionnairePublication . Ladeira, Carina; Carolino, Elisabete; Gomes, Manuel C.; Brito, MiguelThe links between diet and genomic instability have been under investigation for several decades, and evidence suggests a significant causal or preventive role for various dietary factors. This study investigates the influence of macronutrients (calories, protein, and glucides) and micronutrients, such as vitamins and minerals, as assessed by a food frequency questionnaire, on genotoxicity biomarkers measured by cytokinesis-blocked micronucleus assay and comet assay. The results found significant positive and negative correlations. Micronucleus frequency tends to increase with higher intake of caffeine, calcium, magnesium, zinc, and protein (P < .05, Spearman correlation). Calorie and omega-6 intakes are negatively correlated with DNA damage measured by the comet assay. These results are somewhat controversial because some of the correlations found are contrary to dominant views in the literature; however, we suggest that unraveling the association between diet and genetic instability requires a much better understanding of the modulating role of macronutrients and micronutrients.
- Exposição ocupacional a formaldeído: avaliação da exposição e efeitos genotóxicosPublication . Ladeira, Carina; Viegas, Susana; Carolino, Elisabete; Gomes, Mário; Prista, João; Gomes, Manuel Carmo; Brito, MiguelO formaldeído (FA) foi classificado, em 2004, pela International Agency for Cancer Research como agente cancerígeno. Este agente químico ocupa a 25ª posição em toda a produção química dos Estados Unidos da América, com mais de 5 milhões de toneladas produzidas por ano. Devido à sua importância económica e uso diversificado, muitos indivíduos estão expostos profissionalmente a FA. Com o estudo desenvolvido pretendeu‑se avaliar a exposição a FA em dois contextos ocupacionais distintos – na produção de FA e resinas e em laboratórios de anatomia patológica (AP) e relacionar com eventuais efeitos para a saúde, comparando a frequência de micronúcleos (MN) em linfócitos do sangue periférico e em células esfoliadas da mucosa bucal dos trabalhadores expostos a FA com indivíduos não expostos (controlos). Como amostra foram estudados 80 trabalhadores ocupacionalmente expostos a FA: 30 trabalhadores da fábrica de produção de FA e resinas e 50 trabalhadores de 10 laboratórios de AP. Foi constituído um grupo controlo de 85 indivíduos com atividades profissionais que não envolviam a exposição a formaldeído ou qualquer outro agente químico com propriedades genotóxicas. Aplicaram‑se duas metodologias distintas de avaliação ambiental do FA com o objetivo de conhecer a exposição profissional. Compararam‑se os resultados obtidos com os valores limite para a exposição média ponderada (TLV‑TWA=0,75 ppm) e para a concentração máxima (VLE‑CM=0,3 ppm). A totalidade dos laboratórios apresentou resultados superiores ao valor de referência existente para a concentração máxima. Nenhum dos resultados obtidos para a exposição média ponderada foi superior ao valor de referência. O exame macroscópico obteve os valores das concentrações máximas mais elevadas em 90% dos laboratórios. Os valores de MN foram mais elevados nos indivíduos expostos a FA comparativamente com os controlos. No caso dos MN nos linfócitos, a média foi de 3,96 nos expostos e de 0,81 nos não expostos. Os MN nas células esfoliadas da boca apresentaram uma média de 0,96 nos expostos e de 0,16 nos controlos. Os resultados obtidos nesta acção de biomonitorização podem revelar‑se particularmente úteis para as organizações responsáveis em definir os níveis aceitáveis para a exposição humana a FA. ABSTRACT: Since 2004, formaldehyde (FA) has been classified by the International Agency for Cancer Research as a carcinogen. The FA ranks 25th in the overall United States chemical production, with more than 5 million tons produced each year. Due to its economic importance and varied use, many individuals are exposed to FA at their occupational settings. This study aimed to assess the exposure to FA in two occupational settings – FA production factory and pathology anatomy (PA) laboratories – and relate it to possible health effects by comparing frequency of micronuclei (MN) in peripheral blood lymphocytes and exfoliated cells from the oral mucosa of workers exposed to FA with individuals not exposed to this agent (controls). This study was performed in 80 workers occupationally exposed to FA: 30 workers of the FA factory and 50 workers in 10 PA laboratories. The control group comprised 85 subjects without exposure. We have applied two different methodologies for environmental monitoring of FA. The results were compared with the reference to the exposure weighted average (TLV‑TWA = 0.75 ppm) and ceiling concentration (VLE‑MC = 0.3 ppm). All laboratories had results higher than the reference value to CM (1.41 ppm). None of the results obtained for the TWA exposure (0.16 ppm) were higher than the reference value. Macroscopic examination obtained the highest values of CM in 90% of laboratories. MN values were higher in individuals exposed to FA as compared to controls. As for MN in lymphocytes, the average was 3.96 in exposed compared with 0.81 in the unexposed. The MN in exfoliated cells of the buccal mucosa had an average of 0.96 in exposed, compared with 0.16 in controls. The results of this biomonitoring can be particularly useful to organizations responsible for defining acceptable levels for human exposure to FA.
- Environmental and occupational exposure to chemical agents and health challenges I: what message can bring to regulatory science?Publication . Ladeira, CarinaHuman beings live in constant contact with chemical agents—mainly through environmental exposure—and also derived from occupational settings. Environmental exposure is ubiquitous, originating from air, water, and soil. While some chemicals are short-lived in the environment and may elicit no harmful effects in humans, other chemicals bioaccumulate and/or persist for a long time in the environment or the human body due to frequent exposure. However, it is valuable to note that environmental exposure also includes diet, lifestyle, hobbies, and exposure to other substances such as drugs, food additives, pesticides, and nanomaterials, among other daily products, which are currently significant areas of research, such as bisphenols, per- and poly-fluoroalkyl substances (PFAS), micro-nano plastics (MP-NPs), among others. Occupational exposure concerns the potentially harmful exposure to hazardous chemicals in the workplace; however, more specifically, it involves substantial contact with hazardous substances. Possible health effects can arise from these types of exposure, which can be measured and prevented by biomonitoring, and the outcome should be integrated to ensure better regulatory decision-making. This editorial provides a brief overview of the major findings of each of the research published, and taken together which information can give to surveillance health and regulatory science on the future research that should be considered.
- Blood molecular profile to predict genotoxicity from exposure to antineoplastic drugsPublication . Ladeira, Carina; Araújo, Rúben; Ramalhete, Luís; Teixeira, Hélder; Calado, Cecília R. C.Genotoxicity is important information that should be included in human biomonitoring programs. However, the usually applied cytogenetic assays are laborious and time-consuming, the reason why it is critical to developing rapid and economic new methods. The aim of this study was to evaluate if the molecular profile of frozen whole blood, acquired by Fourier Transform Infrared (FTIR) spectroscopy, allows to assess genotoxicity in occupational exposure to antineoplastic drugs, as obtained by the cytokinesis-block micronucleus assay. For that purpose, 92 samples of peripheral blood were studied: 46 samples from hospital professionals occupationally exposed to antineoplastic drugs and 46 samples from workers in academia without exposure (controls). It was first evaluated the metabolome from frozen whole blood by methanol precipitation of macromolecules as haemoglobin, followed by centrifugation. The metabolome molecular profile resulted in 3 ratios of spectral bands, significantly different between the exposed and non-exposed group (p<0.01), and a spectral principal component-linear discriminant analysis (PCA-LDA) model enabling to predict genotoxicity from exposure with 73 % accuracy. After optimization of the dilution degree and solution used, it was possible to obtain a higher number of significant ratios of spectral bands, i.e., 10 ratios significantly different (p<0.001), highlighting the high sensitivity and specificity of the method. Indeed, the PCA-LDA model, based on the molecular profile of whole blood, enabled to predict genotoxicity from exposure with an accuracy, sensitivity, and specificity of 92 %, 93 %, and 91 %, respectively. All these parameters were achieved based on 1 μL of frozen whole blood, in a high-throughput mode, i.e., based on the simultaneous analysis of 92 samples, in a simple and economic mode. In summary, it can be concluded that this method presents a very promising potential for high-dimension screening of exposure to genotoxic substances.
- Spectral biomarkers of genotoxicity from methanol extracts of bloodPublication . Teixeira, Hélder Paz; Ramalhete, Luís; Ladeira, Carina; Calado, CecíliaIt is relevant to develop new monitoring techniques of carcinogenic risk associated to environmental exposition to genotoxic chemicals. The conventional biomonitoring techniques are based on laborious, expensive methods as the ones requiring isolation of lymphocytes from peripheral blood, in vitro cell culture, followed by e.g. cytokinesis-block assay and microscope observation of chromosomal abnormalities. The present work evaluated an infrared spectroscopy method, based on a simple, more economic and high-throughput procedure of analysis of whole blood processed with methanol. It was possible to identify ratios of spectral bands that are statistically different between hospital professionals occupationally exposed to antineoplastic drugs, such as 5-fluorouracil and non-hospital professionals without this exposure. It was also identified ratios of spectral bands which are statistically different between participants presenting lymphocytes with chromosomal abnormalities (as micronucleus, nuclear buds and nucleoplasmatic bridges) and participants not presenting these abnormalities. The infrared spectroscopy-based method presents therefore appealing characteristics to be applied in more intensive and/or large-scale studies of monitoring genotoxic risks.
- HBM4EU chromates study: determinants of exposure to hexavalent chromium in plating, welding and other occupational settingsPublication . Viegas, Susana; Martins, Carla; Bocca, Beatrice; Bousoumah, Radia; Duca, Radu Corneliu; Galea, Karen S.; Godderis, Lode; Iavicoli, Ivo; Janasik, Beata; Jones, Kate; Leese, Elizabeth; Leso, Veruscka; Ndaw, Sophie; van Nieuwenhuyse, An; Poels, Katrien; Porras, Simo P.; Ruggieri, Flavia; Silva, Maria João; Verdonck, Jelle; Wasowicz, Wojciech; Scheepers, Paul T. J.; Santonen, Tiina; Ladeira, Carina; Ribeiro, EdnaWork-related exposures in industrial processing of chromate (chrome plating, surface treatment, and welding) raise concerns regarding the health risk of hexavalent chromium (Cr(VI)). In this study, performed under the HBM4EU project, we focused on better understanding the determinants of exposure and recognising how risk management measures (RMMs) contribute to a reduction in exposure. HBM and occupational hygiene data were collected from 399 workers and 203 controls recruited in nine European countries. Urinary total chromium (U-Cr), personal inhalable and respirable dust of Cr and Cr(VI), and Cr from hand wipes were collected. Data on the RMMs were collected by questionnaires. We studied the association between different exposure parameters and the use of RMMs. The relationship between exposure by inhalation and U-Cr in different worker groups was analysed using regression analysis and found a strong association. Automatisation of Cr electroplating dipping explained lower exposure levels in platers. The use of personal protective equipment resulted in lower U-Cr levels in welding, bath plating, and painting. An effect of wearing gloves was observed in machining. An effect of local exhaust ventilation and training was observed in welding. Regression analyses showed that in platers, exposure to an air level of 5 µg/m3 corresponds to a U-Cr level of 7 µg/g of creatinine. In welders, the same inhalation exposure resulted in lower U-Cr levels reflecting toxicokinetic differences of different chromium species.
- Epigallocatechin-3-gallate (EGCG): an alternative to extenuate occupational risk factors outcomes? An interventional studyPublication . Ladeira, Carina; Pádua, Mário; Ribeiro, EdnaIntroduction: Occupational risk factors are major players in the increased risk of cardiovascular diseases and cancer. Studies support a protective role of Epigallocatechin-3-gallate (EGCG) in disease onset, with associated antioxidant properties and reactive oxygen species production. We aimed to evaluate the in vivo effects of EGCG intake on cardiovascular risk factors, DNA damage, and oxidative DNA damage. Methods: Voluntaries were enrolled in this interventional study with the safeguard of all ethical considerations. Peripheral blood was collected at the beginning and after 90 days of 225 mg EGCG ingestion per day. Lipid profile and liver function parameters were assessed using colorimetric methods. Vitamins A and E in serum were quantified by HPLC–DAD. DNA damage and oxidative DNA damage were assessed through comet assay. Results: Vitamin A, as well as the lipid profile and liver function parameters, were not affected by EGCG intake, whereas serum levels of vitamin E, DNA damage, and DNA oxidative damage increased after EGCG consumption. Discussion/Conclusions: EGCG induces low-level oxidative stress which may trigger protective antioxidant systems associated with vitamin E. Further research is crucial to understand the extent of EGCG effects and its potential as an alternative to extenuate occupational risk factors outcomes.