DGH - Dissertações de mestrado
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Percorrer DGH - Dissertações de mestrado por Domínios Científicos e Tecnológicos (FOS) "Ciências Médicas::Ciências da Saúde"
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- Assessment of genotoxicity biomarkers in the scope of a human biomonitoring study in workers from E-waste management industriesPublication . Lopes Rosário, Rita Isabel; Silva, Maria João; Pina Martins, FranciscoElectrical and electronic waste (e-waste) represents a pressing global challenge with its rapid growth and hazardous composition. This recycling sector often involves inadequate worker safety, exposing e-workers to harmful substances like heavy metals and flame retardants via several routes, causing significant short- and long-term health risks. Human Biomonitoring (HBM) is a useful tool in assessing exposure and associated health outcomes through biomarkers like micronucleus (MN) in blood or epithelial cells, enabling the identification of early biological changes and linking exposure to disease. This HBM study used two assays,- the Buccal Micronucleus Cytome (BMNCyt) assay and the Cytokinesis-Block Micronucleus Cytome (CBMNCyt) assay,- to assess potential genotoxic effects from occupational e-waste exposure. The BMNCyt assay, conducted under the HBM4EU initiative, targets buccal mucosa epithelial cells, a primary barrier against hazardous agents, thus assessing local genotoxic effects. The CBMNCyt assay in peripheral blood lymphocytes, conducted under the PARC Project, reliably measures structural and numerical chromosomal changes, reflecting a systemic effect. This research aimed to assess early biological effects from exposure to pollutants from e-waste in in PBL and buccal epithelial cells of European e-waste workers, comparatively with control groups. The BMNCyt assay showed no significant differences in MN frequency between the exposed and control groups, while the CBMNCyt assay detected significantly increased frequencies of MN in exposed compared with non-exposed groups. Factors like small sample sizes, interindividual differences, and the use of protective equipment might have influenced results. Demographic/lifestyle variables showed differing impacts on MN formation between assays, but also potential influence, thus the importance of their consideration. Concluding, expanding e-waste occupational health research to include more workers/activities within the waste management industry and broader biomonitoring efforts is paramount. Boosting the understanding of health risks associated with those activities will help developing protective measures and mitigation strategies to safeguard the exposed workers’ health.
- Hazard characterisation of bisphenol A alternatives to improve risk assessment for human health: genotoxic and carcinogenic effects in mammalian cellsPublication . Pereira, Maria João Rodrigues; Silva, Maria João; Farinha, CarlosBisphenol A (BPA) is a compound used in the production of epoxy resins, polycarbonate plastics and as an additive (e.g. in thermal paper). It is present in several different products and has been detected both in the environment and in human matrices. BPA is a known endocrine disruptor, with several studies linking it to multiple harmful health effects. Therefore, there is an effort to phase out its use, but also to replace it with alternative substances. Various alternatives are already being used and have been detected in the environment and human matrices. Furthermore, some harmful health effects have also been reported for those substances (albeit not as many as BPA), justifying the need for more research on these alternatives. This thesis is part of the Partnership for the Assessment of Risks from Chemicals (PARC), that prioritized alternatives based on the lack of data on their effects on human health and due to human exposure to them occurring or being likely to occur. This thesis focused on BPS-MAE and BPAP, aiming to contribute to their hazard assessment, through the characterisation of their in vitro genotoxic and carcinogenic potential. The former was assessed for BPS-MAE and BPAP with the Cytokinesis-Block Micronucleus assay, in human peripheral blood lymphocytes. The results suggest that BPS-MAE and BPAP do not have a genotoxic effect at the concentrations and exposure times tested. Genotoxic and non-genotoxic carcinogenicity of BPAP and BPA was ascertained with the Cell Transformation assay, in Bhas 42 cells. BPA was tested to allow inter-laboratory comparison of results and assay optimisation. The results indicate that neither BPAP nor BPA have potential carcinogenic activity at the concentrations and treatment durations tested. The data obtained will help eliminating existing data gaps, aid to improve these alternatives’ risk assessment and contribute to the formulation of legislation, if necessary.
- The mechanism of nonsense-mediated mRNA decay and its playersPublication . Subtil, Catarina; Loison, Luísa; Santos, Rafaela LacerdaNonsense-mediated mRNA decay (NMD) is a post-transcriptional surveillance mechanism harbouring two functions: identification and degradation of transcripts containing premature translation-termination codons (PTC), preventing deleterious effects in the cell; and downregulation of mRNAs in response to cellular needs, maintaining the quality of gene expression. One-third of gene mutations in human genetic diseases, including cancer, are due to nonsense mutations or frameshift that result in transcripts harbouring nonsense codons and can be eliminated by NMD. The several factors involved in this mechanism may act in diverse ways depending on the set of transcripts to be regulated, contributing to the branching of this pathway. Cytoplasmic DIS3 exosome independent 3′-5′ exoribonuclease 2 (DIS3L2) has been reported as one of the factors to induce NMD targets decay. Therefore, this study aims to enlighten how DIS3L2 functions in NMD: i) analyse the correlation between the distinct branches of NMD and cervical and uterus cancer; ii) investigate which branch guides DIS3L2-mediated degradation; and iii) test which region of the NMD/DIS3L2-targets mediate DIS3L2 degradation through a system of hybrid-genes. For our first aim, we detected no correlation between any of the branches of NMD and uterus and cervical cancer. Each factor acts independently. In our second objective, we analysed the mRNA expression of five transcripts, but none displayed a significant alteration in their expression to infer a correlation between DIS3L2 and a particular NMD branch. Relatively to the last aim, we successfully cloned three out of the four constructs but due to time constrictions we could not continue. Nonetheless, further testing is needed to better understand this mechanism and how transcript degradation is mediated, including the diverse factors needed for its activation, which might be the key to future advanced therapeutic strategies.