Rohr Paula, Karen Shimoyama, Francisco Luiza Flávia Veiga, Oliveira Marco Antônio, Dos Santos Neto Martins Fidelis, Silveira Henrique C S
Molecular Oncology Research Center, Barretos Cancer Hospital, Rua Antenor Duarte Vilela, 1331, B. Dr. Paulo Prata, Barretos, SP 14784-390, Brazil.
Campus São Paulo, University of Anhanguera, São Paulo, SP 04119-901, Brazil.
Environ Epigenet. 2024 Apr 20;10(1):dvae005. doi: 10.1093/eep/dvae005. eCollection 2024.
In recent decades, the use of pesticides in agriculture has increased dramatically. This has resulted in these substances being widely dispersed in the environment, contaminating both exposed workers and communities living near agricultural areas and via contaminated foodstuffs. In addition to acute poisoning, chronic exposure to pesticides can lead to molecular changes that are becoming better understood. Therefore, the aim of this study was to assess, through a systematic review of the literature, what epigenetic alterations are associated with pesticide exposure. We performed a systematic review and meta-analysis including case-control, cohort and cross-sectional observational epidemiological studies to verify the epigenetic changes, such as DNA methylation, histone modification and differential microRNA expression, in humans who had been exposed to any type of pesticide. Articles published between the years 2005 and 2020 were collected. Two different reviewers performed a blind selection of the studies using the Rayyan QCRI software. Post-completion, the data of selected articles were extracted and analyzed. Most of the 28 articles included evaluated global DNA methylation levels, and the most commonly reported epigenetic modification in response to pesticide exposure was global DNA hypomethylation. Meta-analysis revealed a significant negative correlation between Alu methylation levels and β-hexachlorocyclohexane, ,-dichlorodiphenyldichloroethane and -dichlorodiphenylethylene levels. In addition, some specific genes were reported to be hypermethylated in promoter regions, such as and , while and were hypomethylated due to pesticide exposure. The expression of microRNAs was also altered in response to pesticides, as miR-223, miR-518d-3p, miR-597, miR-517b and miR-133b that are associated with many human diseases. Therefore, this study provides evidence that pesticide exposure could lead to epigenetic modifications, possibly altering global and gene-specific methylation levels, epigenome-wide methylation and microRNA differential expression.
近几十年来，农业中农药的使用急剧增加。这导致这些物质在环境中广泛扩散，污染了接触农药的工人以及生活在农业区域附近的社区，并通过受污染的食品造成影响。除了急性中毒外，长期接触农药会导致分子变化，对此人们的了解也越来越深入。因此，本研究的目的是通过对文献的系统综述，评估与农药接触相关的表观遗传改变。我们进行了一项系统综述和荟萃分析，纳入病例对照、队列和横断面观察性流行病学研究，以验证接触任何类型农药的人群中的表观遗传变化，如DNA甲基化、组蛋白修饰和微小RNA差异表达。收集了2005年至2020年间发表的文章。两名不同的评审员使用Rayyan QCRI软件对研究进行了盲选。完成后，提取并分析了所选文章的数据。纳入的28篇文章中，大多数评估了全基因组DNA甲基化水平，对农药接触最常报道的表观遗传修饰是全基因组DNA低甲基化。荟萃分析显示，Alu甲基化水平与β-六氯环己烷、滴滴滴和滴滴伊水平之间存在显著负相关。此外，据报道一些特定基因在启动子区域发生高甲基化，如[具体基因1]和[具体基因2]，而[具体基因3]和[具体基因4]由于农药接触发生低甲基化。微小RNA的表达也因农药而改变，如与许多人类疾病相关的miR-223、miR-518d-3p、miR-597、miR-517b和miR-133b。因此，本研究提供了证据表明农药接触可能导致表观遗传修饰，可能改变全基因组和基因特异性甲基化水平、全表观基因组甲基化和微小RNA差异表达。
