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- 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.
- 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.
- Importância do polimorfismo OGG1 Ser326Cys no estudo dos efeitos para a saúde que resultam da exposição ocupacional a genotóxicos: o caso da exposição a antioneoplásicosPublication . Ladeira, Carina; Viegas, Susana; Pádua, Mário; Carolino, Elisabete; Gomes, Manuel C.; Brito, MiguelO ensaio cometa é um dos ensaios de avaliação de genotoxicidade mais promissores de avaliação do risco humano, sendo recomendado para a monitorização de populações com exposição crónica a agentes genotóxicos. Os laboratórios são ambientes profissionais em que os trabalhadores podem encontrar-se expostos a agentes químicos. As drogas antineoplásicas são agentes químicos que são considerados carcinogénicos e, desta forma, medidas de protecção especiais devem ser adoptadas. O objectivo desta comunicação é contribuir para o desenvolvimento de um programa de biomonitorização que inclui a avaliação de genotoxicidade relacionada com biomarcadores de susceptibilidade genética.
- Effects of exposure to formaldehyde and tobacco smoking on genotoxicity biomarkersPublication . Ladeira, Carina; Gomes, Manuel C.; Brito, MiguelFormaldehyde (FA) is a colour less gas widely used in the industry and hospitals as an aqueous solution, formalin. It is extremely reactive and induces various genotoxic effects in proliferating cultured mammalian cells. Tobacco smoke has been epidemiologically associated to a higher risk of development of cancer, especially in the oral cavity, larynx and lungs, as these are places of direct contact with many carcinogenic tobacco’s compounds. Approximately 90% of human cancers originate from epithelial cells. Therefore, it could be argued that oral epithelial cells represent a preferred target site for early genotoxic events induced by carcinogenic agents entering the body via inhalation and ingestion. The cytokinesis-blocked micronucleus assay (CBMN) in human lymphocytes is one of the most commonly used methods for measuring DNA damage, namely the detection of micronucleus, nucleoplasmic bridges, and nuclear buds.
- Exposição profissional a formaldeído em laboratórios de anatomia patológica: que realidade em Portugal?Publication . Ladeira, Carina; Viegas, Susana; Carolino, Elisabete; Prista, João; Gomes, Manuel C.; Brito, MiguelO formaldeído é um gás incolor, solúvel na água e que reage rapidamente com o local de contacto. É utilizado nos laboratórios de Anatomia Patológica (AP) como fixador de células e tecidos - importante local de exposição ocupacional ao formaldeído, nomeadamente por médicos patologistas, técnicos de AP e auxiliares de acção médica. Objectivos do estudo: conhecer a exposição a formaldeído nos laboratórios hospitalares de Anatomia Patológica em Portugal; comparar a frequência de MN em linfócitos do sangue periférico e em células esfoliadas da mucosa bucal dos trabalhadores expostos a formaldeído nos laboratórios de AP – patologistas, técnicos de AP e auxiliares com controlos.
- Effects of the interaction of tobacco smoke and alcohol consumption on buccal micronucleus in workers exposed occupationally to formaldehydePublication . Ladeira, Carina; Viegas, Susana; Carolino, Elisabete; Prista, João; Gomes, Manuel C.; Brito, MiguelOccupational exposure to formaldehyde (FA) has been shown to induce nasopharyngeal cancer and has been classified as carcinogenic to humans (group 1) on the basis of sufficient evidence in humans. Tobacco smoke has been associated to a higher risk of development of cancer, especially in the oral cavity, larynx and lungs, as these are places of direct contact with many carcinogenic tobacco’s compounds. Alcohol is a recognized agent that influence cells in a genotoxic form, been citied as a strong agent with potential in the development of carcinogenic lesions. Epidemiological evidence points to a strong synergistic effect between cigarette smoking and alcohol consumption in the induction of cancers in the oral cavity. Approximately 90% of human cancers originate from epithelial cells. Therefore, it could be argued that oral epithelial cells represent a preferred target site for early genotoxic events induced by carcinogenic agents entering the body via inhalation and ingestion. The MN assay in buccal cells was also used to study cancerous and precancerous lesions and to monitor the effects of a number of chemopreventive agents.
- Relation between DNA damage measured by comet assay and OGG1 Ser326Cys polymorphism in antineoplastic drugs biomonitoringPublication . Ladeira, Carina; Viegas, Susana; Pádua, Mário; Carolino, Elisabete; Gomes, Manuel C.; Brito, MiguelAntineoplastic drugs are hazardous chemical agents used mostly in the treatment of patients with cancer, however health professionals that handle and administer these drugs can become exposed and develop DNA damage. Comet assay is a standard method for assessing DNA damage in human biomonitoring and, combined with formamidopyrimidine DNA glycosylase (FPG) enzyme, it specifically detects DNA oxidative damage. The aim of this study was to investigate genotoxic effects in workers occupationally exposed to cytostatics (n = 46), as compared to a control group with no exposure (n = 46) at two Portuguese hospitals, by means of the alkaline comet assay. The potential of the OGG1 Ser326Cys polymorphism as a susceptibility biomarker was also investigated. Exposure was evaluated by investigating the contamination of surfaces and genotoxic assessment was done by alkaline comet assay in peripheral blood lymphocytes. OGG1 Ser326Cys (rs1052133) polymorphism was studied by Real Time PCR. As for exposure assessment, there were 121 (37%) positive samples out of a total of 327 samples analysed from both hospitals. No statistically significant differences (Mann-Whitney test, p > 0.05) were found between subjects with and without exposure, regarding DNA damage and oxidative DNA damage, nevertheless the exposed group exhibited higher values. Moreover, there was no consistent trend regarding the variation of both biomarkers as assessed by comet assay with OGG1 polymorphism. Our study was not statistically significant regarding occupational exposure to antineoplastic drugs and genetic damage assessed by comet assay. However, health professionals should be monitored for risk behaviour, in order to ensure that safety measures are applied and protection devices are used correctly.
- Evaluation of the influence of the ADH3 ILE349VAL polymorphism in the frequency of genotoxicity biomarkers in workers exposed to formaldehyde and tobacco smokingPublication . Ladeira, Carina; Gomes, Manuel C.; Brito, MiguelFormaldehyde (FA) is a colourless gas widely used in the industry and hospitals as an aqueous solution, formalin. It is extremely reactive and induces various genotoxic effects in proliferating cultured mammalian cells. Tobacco smoke has been epidemiologically associated to a higher risk of development of cancer, especially in the oral cavity, larynx and lungs, as these are places of direct contact with many carcinogenic tobacco’s compounds. Genetic polymorphisms in enzymes involved in the metabolism are very important and can make changes in the individual susceptibility to disease. Alcohol dehydrogenase class 3 (ADH3), also known as formaldehyde dehydrogenase dependent of glutathione, is the major enzyme involved in the formaldehyde oxidation, especially in the buccal mucosa. The polymorphism in study is a substitution of an isoleucine for a valine in codon 349. The cytokinesis-blocked micronucleus assay (CBMN) in human lymphocytes is one of the most commonly used methods for measuring DNA damage, namely the detection of micronucleus, nucleoplasmic bridges, and nuclear buds, classified as genotoxicity biomarkers.
- Interaction of formaldehyde and tobacco smoking in the frequency of micronucleus and the XRCC3 Thr241Met polymorphismPublication . Ladeira, Carina; Gomes, Manuel C.; Brito, MiguelFormaldehyde is classified by IARC as carcinogenic to humans (nasopharyngeal cancer). Tobacco smoke has been epidemiologically associated to a higher risk of development of cancer, especially in the oral cavity, larynx and lungs, as these are places of direct contact with many carcinogenic tobacco’s compounds. XRCC3 is involved in homologous recombination repair of cross-links and chromosomal double-strand breaks (Thr241Met polymorphism). The aim of the study is to determine whether there is an in vivo association between genetic polymorphism of the gene XRCC3 and the frequency of genotoxicity biomarkers in subjects exposed or not to formaldehyde and with or without tobacco consumption.
- Effects of age and gender on peripheral lymphocyte micronucleusPublication . Ladeira, Carina; Viegas, Susana; Gomes, Manuel C.; Brito, MiguelAging in humans appears to be associated with genetic instability. The cytokinesis-blocked micronucleus assay (CBMN) is a comprehensive method for measuring chromosome breakage, DNA misrepair, chromosome loss, non-disjunction, necrosis, apoptosis and cytostasis. Age and gender are the most important demographic variables affecting the micronucleus (MN) index and studies report frequencies in females being greater than those in males by a factor of 1.2 to 1.6 depending on the age group. It has been shown that a higher MN frequency directly corresponds to a decreased efficiency of DNA repair and increased genome instability.