The impact of chemical exposure on the transcriptome of formal and informal workers

Author(s)

Fernanda Junqueira Salles

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Faculdade de Saúde Pública (FSP/CIR)
• Defense date: 2023-11-22

Examining board members

Kelly Polido Kaneshiro Olympio; Solange Cristina Garcia; Marcelo Macedo Rogero; Liliane Reis Teixeira

• Advisor: Kelly Polido Kaneshiro Olympio

Abstract

Introduction: Chemical exposures may vary in geographically distinct populations, with different habits, lifestyles, and individual characteristics. Objectives: a) to determine potentially toxic elements\' (EPTs: As, Cd, Cr, Cu, Hg, Mn, Ni, Pb, Sb, Sn, and Zn) in the urine of the population of Limeira, and in jewelry pieces and soldering powder; b) determine the PTEs concentrations in the participants\' blood from Limeira and Volta Redonda municipalities; c) investigate disease risks associated with occupational exposure; d) to evaluate the impact of occupational exposure on gene expression profile. Methods: The exposed group was composed of informal workers who perform soldering of jewelry inside their houses in the city of Limeira, SP; and formal workers from a steel company in the city of Volta Redonda, RJ. Control participants were recruited from the same neighborhoods without occupational chemical exposure. Blood samples were collected for blood glucose, insulin, lipid profile, and PTE determinations, and for transcriptomic analysis. In Limeira, PTE concentration in urine was also determined. RNA was extracted and hybridized to Agilent SurePrint G3 Human Gene Expression 8x60K v2 Microarray for transcriptomics analysis. Pre-processing, statistical, and pathway analysis were performed in GeneSpring GX software. All participants completed questionnaires about household risk, reported morbidity, and occupational exposure. The association between PTEs exposure and health outcomes was tested by a multivariable robust Poisson regression model. Results: 16 up- and 33 down-regulated genes (fold-change > 2) were observed in the informal workers. Pathway analysis revealed genes enriched in inflammatory process (MAPK, Toll-like receptor, and NF-kappa B chemokine signaling pathways). In formal workers, 20 up- and 50 down-regulated genes were found with pathways related to immune response and atherosclerosis development. The gene IFI27 which has been associated with various types of cancer was the only one commonly differentially expressed between informal and formal workers. Informal jewelry production in Limeira increased exposure to Cd, with significantly higher concentrations in the urine and blood of informal exposed workers compared to controls. Furthermore, a positive association was observed between blood Cd concentrations and glycemia. The blood concentration of As and Pb were also Participants with Pb concentrations higher than 2.6 μg dL-1 showed a prevalence of neurological manifestations 2.3 times higher (95% CI: 1.17 - 4.58; p = 0.02) than those with lower lead concentrations. No significant differences were observed between formal workers from Volta Redonda and their control group, probably, because of the use of individual protection equipment and the environmental pollution in the region. Conclusion: Differences in gene expression related to occupational exposure are mainly associated with inflammation and immune response. The results suggest that prolonged occupational exposure to toxic elements could lead to negative health outcomes, such as higher prevalence of neurological manifestations. These exploratory results are a starting point for analysis in sensitive and understudied populations, especially in developing countries. Further analysis should be carried out to investigate its direct effects and to validate causal associations. (AU)

• FAPESP's process: 17/25424-9 - The impact of chemical exposure on the transcriptome of informal workers
• Grantee: Fernanda Junqueira Salles
• Support Opportunities: Scholarships in Brazil - Doctorate