Transcriptional Dysregulation of Histone Methyltransferase Genes and Chromosomal Instability Associated With Chronic Pesticide Exposure

ABSTRACT

Occupational pesticide exposure is a significant environmental health concern associated with genomic instability. Histone methyltransferases including SMYD2 , SMYD3 , EZH2 , and SETD8 participate in chromatin regulation and DNA damage responses, but their transcriptional profiles in exposed populations remain poorly understood. To evaluate chromosomal instability and expression of histone methyltransferase genes in agricultural workers. A cross‐sectional biomonitoring study included 137 participants classified as directly exposed ( n  = 62), indirectly exposed ( n  = 41), or putative non‐exposed ( n  = 34). Buccal epithelial cells were collected for micronucleus (MN) analysis and gene expression profiling. Relative mRNA expression levels of SMYD2 , SMYD3 , EZH2 , and SETD8 were quantified by RT‐qPCR. Statistical analyses included ANOVA, correlation analyses, and multivariable regression models. MN frequency increased significantly according to exposure status, with directly exposed workers exhibiting the highest levels of chromosomal damage (7.0 ± 1.2 MN/2000 cells), followed by indirectly exposed individuals (3.9 ± 1.0 MN/2000 cells) and putative non‐exposed participants (2.1 ± 0.6 MN/2000 cells) ( p  < 0.001). Consistent use of personal protective equipment was associated with lower MN frequencies among directly exposed workers ( p  < 0.001). Gene expression analyses demonstrated increased EZH2 and SETD8 expression in exposed groups, whereas SMYD3 exhibited greater transcriptional variability than SMYD2 . Significant positive correlations between MN frequency and expression levels of EZH2 , SETD8 , SMYD3 , and SMYD2 were observed among directly exposed workers (all p  < 0.05). Chronic occupational pesticide exposure is associated with chromosomal instability and altered expression of genes involved in chromatin regulation. These findings support their utility as potential exposure biomarkers.