Effects of pesticide exposure on oxidative stress and DNA methylation urinary biomarkers in Czech adults and children from the CELSPAC-SPECIMEn cohort
Janoš, Tomáš; Ottenbros, Ilse; Bláhová, Lucie; Šenk, Petr; Šulc, Libor; Pálešová, Nina; Sheardová, Jessica; Vlaanderen, Jelle; Čupr, Pavel
(2023) Environmental Research, volume 222
(Article)
Abstract
Current-use pesticide (CUP) exposure occurs mainly through diet and environmental application in both agricultural and urban settings. While pesticide exposure has been associated with many adverse health outcomes, the intermediary molecular mechanisms are still not completely elucidated. Among others, their roles in epigenetics (DNA methylation) and DNA damage due to
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oxidative stress are presumed. Scientific evidence on urinary biomarkers of such body response in general population is limited, especially in children. A total of 440 urine samples (n = 110 parent-child pairs) were collected during the winter and summer seasons in order to describe levels of overall DNA methylation (5-mC, 5-mdC, 5-hmdC, 7-mG, 3-mA) and oxidative stress (8-OHdG) biomarkers and investigate their possible associations with metabolites of pyrethroids (3-PBA, t/c-DCCA), chlorpyrifos (TCPY), and tebuconazole (TEB-OH). Linear mixed-effects models accounting for intraindividual and intrahousehold correlations were utilized. We applied false discovery rate procedure to account for multiplicity and adjusted for potential confounding variables. Higher urinary levels of most biological response biomarkers were measured in winter samples. In adjusted repeated measures models, interquartile range (IQR) increases in pyrethroid metabolites were associated with higher oxidative stress. t/c-DCCA and TCPY were associated with higher urinary levels of cytosine methylation biomarkers (5-mC and/or 5-mdC). The most robust association was observed for tebuconazole metabolite with 3-mA (-15.1% change per IQR increase, 95% CI = -23.6, -5.69) suggesting a role of this pesticide in reduced demethylation processes through possible DNA glycosylase inhibition. Our results indicate an urgent need to extend the range of analyzed environmental chemicals such as azole pesticides (e.g. prothioconazole) in human biomonitoring studies. This is the first study to report urinary DNA methylation biomarkers in children and associations between CUP metabolites and a comprehensive set of biomarkers including methylated and oxidized DNA alterations. Observed associations warrant further large-scale research of these biomarkers and environmental pollutants including CUPs.
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Keywords: Current-use pesticides (CUPs), DNA methylation, Epigenetics, Oxidative stress, Urine, General Environmental Science, Biochemistry
ISSN: 0013-9351
Publisher: Academic Press Inc.
Note: Funding Information: This project received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No 733032 , grant agreement No 857340 , grant agreement No 874627 and grant agreement No 857560 . The authors thank Research Infrastructure RECETOX RI (No LM2018121) financed by the Ministry of Education, Youth and Sports , and Operational Programme Research, Development and Innovation – project CETOCOEN EXCELLENCE (No CZ.02.1.01/0.0/0.0/17_043/0009632 ) for supportive background. This publication reflects only the author's view and the European Commission is not responsible for any use that may be made of the information it contains. We would like to thank Richard Hůlek, Mazen Ismael, Zuzana Luhová and Jiří Bilík from RECETOX Information systems and data services for the preparation of a data warehouse and infastructure to store and manage the CELSPAC-SPECIMEn study data. We thank Lenka Andrýsková for her help when addressing the ethical aspects of the study. The authors thank Ondřej Mikeš for his help with the preparation of exposure questionnaires. The authors thank Ludmila Šebejová, Zuzana Jašková and Lenka Kociánová from CELSPAC Biobank for support with the preparation of urine aliquots and for storing samples in the CELSPAC biobank facility. In addition, we are grateful to Roman Prokeš and Jakub Vinkler for collecting the samples. Funding Information: This project received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No 733032, grant agreement No 857340, grant agreement No 874627 and grant agreement No 857560. The authors thank Research Infrastructure RECETOX RI (No LM2018121) financed by the Ministry of Education, Youth and Sports, and Operational Programme Research, Development and Innovation – project CETOCOEN EXCELLENCE (No CZ.02.1.01/0.0/0.0/17_043/0009632) for supportive background. This publication reflects only the author's view and the European Commission is not responsible for any use that may be made of the information it contains. We would like to thank Richard Hůlek, Mazen Ismael, Zuzana Luhová and Jiří Bilík from RECETOX Information systems and data services for the preparation of a data warehouse and infastructure to store and manage the CELSPAC-SPECIMEn study data. We thank Lenka Andrýsková for her help when addressing the ethical aspects of the study. The authors thank Ondřej Mikeš for his help with the preparation of exposure questionnaires. The authors thank Ludmila Šebejová, Zuzana Jašková and Lenka Kociánová from CELSPAC Biobank for support with the preparation of urine aliquots and for storing samples in the CELSPAC biobank facility. In addition, we are grateful to Roman Prokeš and Jakub Vinkler for collecting the samples. Publisher Copyright: © 2023 The Authors
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