Impact of exposure to methylmercury (MeHg) on epigenetic status and telomere length, as well as their interactions, in individuals from riparian Amazonian communities exposed chronically to metal, via diet

• Grant number: 20/08260-5
• Support Opportunities: Regular Research Grants
• Duration: August 01, 2021 - January 31, 2022
• Field of knowledge: Health Sciences - Pharmacy - Toxicological Analysis
• Principal Investigator: Gustavo Rafael Mazzaron Barcelos
• Grantee: Gustavo Rafael Mazzaron Barcelos
• Host Institution: Instituto de Saúde e Sociedade (ISS). Universidade Federal de São Paulo (UNIFESP). Campus Baixada Santista. Santos , SP, Brazil
• Associated researchers: Fernando Barbosa Júnior
• Associated scholarship(s): 21/11563-2 - Validation of methodologies associated with telomeric size assessment in riverine Amazonian communities exposed to methylmercury via diet, BP.TT

Abstract

Epidemiological studies demonstrate that mercury (Hg), especially methylmercury (MeHg), can induce oxidative stress, systemic inflammation and DNA damage; in addition, recent studies suggest that exposure to metal is also related to changes in epigenetic status. However, there is still a gap regarding how exposure to Hg may impact the expression of genes related to the DNA methylation profile and the expression of miRNAs, which can cause changes in the expression of several genes and, consequently, modulate the toxicity induced by exposure to the metal. Likewise, there is a scarcity of studies in the literature related to telomere senescence induced by exposure to MeHg. In this context, the present study aims to assess the impact of exposure to Hg on the epigenetic profile and on telomere length of peripheral blood leukocytes, in Amazonian riverside communities exposed to MeHg, via diet. Concentrations of the metal (and its chemical species) in blood, plasma, urine and hair will be determined by LC-ICP-MS. Estimation of the global DNA methylation will be evaluated by LINE-1 pyrosequencing; the expression of the DNMT1 and DNMT3A genes (quantification of mRNAs) and of miRNAs associated with them, as well as the quantification of telomere length will be determined by RT-qPCR and qPCR, respectively. Thus, it is expected that the obtained results will assist in a better understanding of the molecular mechanisms related to the interactions between the metal and the various epigenetic events, as well as its possible modulation in maintaining of telomeres length, as well as suggesting the use of potential new biomarkers that precede the adverse effects associated with exposure to MeHg. (AU)