Evaluation of DNA Methylation Changes and Micronuclei in Workers Exposed to a Construction Environment

Abstract

Methylation levels in tumor-suppressor genes and repetitive sequences have previously been used to study the relationship between environmental air pollution and epigenetic changes related to cancer. In this study, we measured the methylation profiles of the promoter regions CDKN2A, MLH1 and APC and the repetitive sequence LINE-1 in 59 workers exposed to the construction environment and in 49 unexposed workers. We also evaluated the micronuclei frequency and levels of trace elements in the blood of all workers. We evaluated of levels of particulate matter and polycyclic aromatic hydrocarbons (PAHs) at the construction site to characterize the environmental exposure. Our findings demonstrated that exposed workers exhibited significantly higher average levels of promoter methylation of CDKN2A, APC, and MLH1 genes and increased hypomethylation of the LINE-1 in comparison to unexposed workers (all p < 0.05). A higher frequency of micronuclei was observed in the exposed group (2 ± 2) compared to the unexposed group (1 ± 1) with p < 0.001. High levels of particulate matter (51–841 μg/m3) and some PAHs were found in samples from the construction environment. In summary, we provide evidence of increased DNA damage and altered DNA methylation of exposed workers, suggesting that genomic approaches to biomonitoring may be an effective way of estimating future cancer risk for construction workers.

Induction of Innate Immune Memory by Engineered Nanoparticles in Monocytes/Macrophages: From Hypothesis to Reality

“…In another study, despite no significant difference in global DNA methylation, it was possible to observe DNA methylation changes in the promoter CpG regions of genes of enzymes involved in the epigenetic regulation, DNA repair (i.e., DNMT1, HDAC4, ATM), and gene of TGF-β repressor (SKI) in blood cells of workers exposed to multi-walled carbon nanotubes (MWCNT) with respect to unexposed control individuals ( 68 ). Furthermore, workers exposed to particulate matter and polycyclic aromatic hydrocarbons exhibited, in their peripheral blood leukocytes, significantly higher average levels of methylation at the promoter of tumor-suppressor genes, such as CDKN2A, APC, and MLH1, and significant hypomethylation at the repetitive DNA sequence LINE-1 (a sequence involved in DNA folding/packaging) in comparison to unexposed workers ( 69 ).…”

Global and gene‐specific promoter methylation, and micronuclei induction in lead‐exposed workers: A cross‐sectional study

“…Similar to our observation, Line‐1 hypomethylation in peripheral lymphocytes were associated with MN frequency among polycyclic aromatic hydrocarbon‐exposed workers (Duan et al, 2013). Another report (Silva et al, 2019) also found that Line‐1 methylation and MN frequency were negatively correlated among workers exposed to a construction environment. MN formation was reported to be induced epigenetically via the loss of DNA methylation (Luzhna et al, 2013).…”

Toxicomethylomics revisited: A state-of-the-science review about DNA methylation modifications in blood cells from workers exposed to toxic agents

“…Silva et al ( 111 ) studied CDKN2A, MLH1 , and APC promoter methylation and LINE-1 as a surrogate marker of global methylation in 59 workers exposed to the construction environment and in 49 unexposed workers. They observed higher average levels of methylation for all three genes and hypomethylation of the LINE-1.…”