Individual DNA Methylation Pattern Shifts in Nanoparticles-Exposed Workers Analyzed in Four Consecutive Years

Abstract

A DNA methylation pattern represents an original plan of the function settings of individual cells and tissues. The basic strategies of its development and changes during the human lifetime are known, but the details related to its modification over the years on an individual basis have not yet been studied. Moreover, current evidence shows that environmental exposure could generate changes in DNA methylation settings and, subsequently, the function of genes. In this study, we analyzed the effect of chronic exposure to nanoparticles (NP) in occupationally exposed workers repeatedly sampled in four consecutive years (2016–2019). A detailed methylation pattern analysis of 14 persons (10 exposed and 4 controls) was performed on an individual basis. A microarray-based approach using chips, allowing the assessment of more than 850 K CpG loci, was used. Individual DNA methylation patterns were compared by principal component analysis (PCA). The results show the shift in DNA methylation patterns in individual years in all the exposed and control subjects. The overall range of differences varied between the years in individual persons. The differences between the first and last year of examination (a three-year time period) seem to be consistently greater in the NP-exposed subjects in comparison with the controls. The selected 14 most differently methylated cg loci were relatively stable in the chronically exposed subjects. In summary, the specific type of long-term exposure can contribute to the fixing of relevant epigenetic changes related to a specific environment as, e.g., NP inhalation.

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

“…They reported hypomethylation at 341 CpG sites and hypermethylation of 364, with leading hits mapping to genes involved in pathways such as immune function and xenobiotic detoxification. More recently, in 2021 Rossnerova et al ( 91 ) reported their findings from a longitudinal study where they analyzed DNA methylation in leukocytes from 10 participants occupationally exposed to nanoparticles and 4 non-exposed controls over the course of 4 years. While they observed methylation changes within both groups, these were more pronounced in the exposed subjects, which they hypothesized to be part of adaptation to chronic nanoparticle exposure.…”

“…During this time their exposure levels decreased, and subsequently they reported that LINE-1 methylation levels increased in 2013 compared to 2009 while hMLH1 methylation levels decreased. On the other hand, Rossnerova et al ( 91 ) reported what they call a “higher stability” in five differentially methylated CpG sites evaluated four times annually in 10 workers exposed to nanoparticles, suggesting an enforcement of epigenetic changes through continuous exposure. As these results suggest dynamic changes in DNA methylation in response to exposure levels, which are therefore likely to fluctuate over the lifecourse, they raise some important questions: how transitory are the observed global hypomethylation and gene-specific hypermethylation within exposed individuals?…”

Genome-Wide DNA Methylation in Policemen Working in Cities Differing by Major Sources of Air Pollution

“…We hypothesize that the discrepancies between the groups may be related to low sample numbers in CB. On the other hand, the differences in cell proportion can also be an important regulatory mechanism in response to the environment [33,34].…”

Nanosafety: An Evolving Concept to Bring the Safest Possible Nanomaterials to Society and Environment

“…The increasing number of studies demonstrating the epigenetic alterations resulting from nanomaterial exposure still lacks a connection with potential health risks. This is due to the unavailability of epigenetic modifications in epidemiological studies, except for only a few related to workplace nanomaterial exposure [ 123 , 132 , 141 , 142 , 143 ]. Like nanogenotoxicity, the assessment of the epigenetic toxicity of nanomaterials is mostly based on in vitro followed by in vivo (mice or rats) models ( Figure 6 ).…”