Exposure to Toxic Metals in the Amazon: Impacts on Telomeric Stability, Gene Expression and Epigenetics in Riverine Populations

• Grant number: 25/10516-1
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: September 01, 2025
• End date: May 31, 2028
• Field of knowledge: Health Sciences - Pharmacy - Toxicological Analysis
• Principal Investigator: Fernando Barbosa Júnior
• Grantee: Lucas Cassulatti dos Santos
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 18/24069-3 - ReSEARCH: Recognizing Signatures of the Exposome to Anticipate the Risks for a Continuous Health, AP.TEM

Abstract

Riverine populations of the Amazon are chronically exposed to toxic metals such as mercury (Hg), lead (Pb), arsenic (As), and cadmium (Cd), primarily through their traditional diet, which is rich in fish and locally grown products. This exposure poses a threat to genomic integrity and may contribute to accelerated cellular aging. Telomeres-repetitive DNA regions located at the ends of chromosomes-play a crucial role in protecting genetic material and maintaining chromosomal stability. Their shortening is considered a biological marker of aging and can be influenced by oxidative stress, inflammation, and dysfunction in DNA repair pathways, all of which are mechanisms potentially triggered by environmental exposures.This cross-sectional study aims to investigate the effects of toxic metal exposure on telomere stability, gene expression, and epigenetic patterns in Amazonian riverine populations. A total of 1,000 adult individuals living in the states of Pará (Tapajós River region and Amazonas) and Amazonas (Amanã and Mamirauá Reserves and Tefé National Forest) will be analyzed. Blood concentrations of Hg, Pb, As, and Cd will be determined by inductively coupled plasma mass spectrometry (ICP-MS). Telomere length in leukocytes will be assessed by real-time PCR (qPCR), along with the expression of shelterin complex genes (TERF1, TERF2, TINF2, POT1, ACD, and RAP1GAP), telomerase (hTERT), and genes involved in DNA repair (ATM and ATR). In addition, the methylation profile of the hTERT gene promoter will be investigated as an epigenetic marker.By integrating molecular, genomic, and epigenetic data, this study aims to elucidate the mechanisms by which chronic exposure to toxic metals may compromise telomere integrity and contribute to senescence processes and chronic diseases. The findings may inform public policies on environmental health and strengthen toxicogenomics in socio-environmentally vulnerable contexts in the Amazon. (AU)