Effect of Pesticides Exposure on Oxidative Stress and Epigenetic Changes Biomarkers in Czech Adults and Children from the CELSPAC-SPECIMEn Cohort

BACKGROUND AND AIM: Pesticides exposure occurs through diet and environmental application readily in both agricultural and urban settings. While pesticides exposure has been associated with many health effects, the question of the adverse outcome pathways is still not clearly answered. Among various molecular mechanisms linked to pesticide-induced chronic diseases, DNA damage due to oxidative stress and their role in epigenetics seems to be of great importance. Thus, we have explored the associations between pesticide metabolites and biomarkers of oxidative stress and epigenetic changes in urine samples from Czech adults and children population during two seasons. METHODS: A total of 440 adult-child pairs urine samples were collected during winter and summer season of 2019-2020. Twelve current-use pesticides or their metabolites were measured in urine as well as 8-hydroxydeoxyguanosine and five methylated DNA bases as biomarkers of oxidative stress and epigenetic changes, respectively. To examine the associations, linear mixed effect models accounting for intraindividual and intrahousehold correlations were utilized. We have applied false discovery rate procedure (FDR) to account for multiplicity and have adjusted for several potential confounding variables. RESULTS: In fully adjusted single exposure models, pyrethroids, chlorpyrifos and tebuconazole metabolites were associated with changes in both oxidative stress and epigenetic biomarkers. In the final fully adjusted multiple exposure model, the greatest effect estimate was observed for chlorpyrifos metabolite which interquartile range change was associated with 15.1 % increase (FDR adjusted 95% confidence interval = 1.16, 31.0) in 5-methyl cytosine biomarker concentration. CONCLUSIONS: Our findings showed some significant associations between urinary metabolites of current-use pesticides and oxidative stress biomarker and methylated DNA bases measured in human urine of general population. These findings suggest potential use of oxidative stress and epigenetic changes biomarkers in future epidemiological studies linking exposure to pesticides and health outcomes. KEYWORDS: pesticides exposure, chlorpyrifos, oxidative stress, epigenetic, DNA methylation