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Integrating biomonitoring and omics approaches for predicting adverse health effects induced by methylmercury, in Amazonian riverside communities exposed to the metal, via diet


Epidemiological studies showed that exposure to mercury (Hg), especially to methylmercury (MeHg), is associated with changes in biochemical parameters associated with nutritional status, with disturbances in the cellular redox state, leading to oxidative damage of macromolecules, such as lipids, proteins and DNA; in addition, recent studies suggest that metal exposure is also associated with increased telomeric instability and changes in epigenetic status. However, there are no studies that assessed the impact of genetic polymorphisms associated with folate and homocysteine metabolism on the alterations in these parameters induced by exposure to MeHg; also, it is not established the interactions between the expression of several genes associated with DNA damage signaling and genetic polymorphisms of enzymes involved in the DNA repair pathways can modulate the genotoxicity induced by MeHg; still, there is no description on how exposure to the metal can increase telomeric instability, as well as the interaction of miRNAs that target the genes that constitute the shelterin. Finally, there is still a gap about the mechanisms by which exposure to MeHg is associated with changes in the DNA methylation profile and its interactions with miRNAs, thus modulating the metal-induced toxicity. In this context, the present study aims to assess the impact of metal exposure on various parameters associated with folate and homocysteine metabolism, with redox state, with DNA and telomeres stability, as well as with epigenetic profile, in exposed Amazonian riverside communities exposed to metal, via fish consumption. Metal concentrations (and its chemical species) will be determined in blood, plasma, urine and hair by LC-ICP-MS and several biochemical parameters related to oxidative stress will be quantified by LC-MS/MS. Biochemical and nutritional parameters associated with lifestyle and diet (especially folic acid and B vitamins) will be quantified by spectrophotometry and chemiluminescence. Genomic instability will be monitored by quantification of urinary 8-OHdG, by comet and micronucleus cytome assay in oral mucosal exfoliative cells (BMNCyt), while telomere size, expression of genes associated with sheleterin and their associations with miRNAs will be quantified by qPCR. The evaluation of the global DNA methylation profile will be assessed by LINE-1 pyrosequencing, and the quantification of the expression of DNMT1 and DNMT3A genes and related miRNAs will be performed by TaqMan assays (qPCR). Thus, it is expected that the results obtained will help to better understand the molecular mechanisms related to the interactions between the metal and genetic and epigenetic events, establishing strategies to minimize adverse health events induced by exposure to the metal. (AU)

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