Gene Expression Under Attack: The Hidden Effect of Pesticides

Resumo

Brazil ranks among the world’s leading consumers of pesticides due to intensive agricultural practices, resulting in widespread occupational exposure among rural workers. This exposure occurs during various stages of crop management and is often worsened by the improper or absent use of Personal Protective Equipment (PPE). Several pesticides are classified by the International Agency for Research on Cancer (IARC) as potentially mutagenic, raising serious concerns regarding their long-term health effects. OBJECTIVE: This study aimed to investigate, through an in-silico approach, changes in gene expression profiles associated with occupational exposure to pesticides among agricultural workers in Goiás, Brazil. Using curated chemical-gene interaction data from the Comparative Toxicogenomics Database (CTD), we performed functional enrichment analyses to identify affected genes, molecular pathways, and interaction networks. Additionally, we explored potential links between genetic susceptibility and health-related outcomes. METHODS: Pesticides were selected based on previous studies conducted with rural populations in Goiás, focusing on the most frequently used active ingredients. Sensitive genes were extracted from the CTD, prioritizing interactions involving human cells and associated with altered gene expression. After filtering for duplicates and excluding unspecific interactions, the dataset underwent enrichment analysis via the Metascape platform, incorporating GO, KEGG, and Reactome databases, with Benjamini-Hochberg correction (p < 0.01). Gene-pathway-pesticide relationships were visually represented using a Sankey diagram generated in RStudio. RESULTS AND CONCLUSION: Chronic pesticide exposure resulted in marked gene expression alterations. Pathways such as “MAPK signaling,” “Response to oxidative stress,” and “Cytokine signaling in the immune system” were upregulated, involving genes like IL6, NFKB1, TNF, HMOX1, and VEGFA, linked to inflammation and oxidative stress. Conversely, downregulation was observed in pathways such as “PI3K-Akt signaling,” “Apoptosis,” and “DNA damage response,” particularly affecting TP53, BAX, CASP3, CASP9, and BRCA1, indicating compromised cellular integrity. These findings highlight the molecular risks correlated to chronic pesticide exposure and underscore the need for further studies and public health interventions.