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

Andrea Rossnerova,Stepanka Dvorackova,Jaroslav A Hubacek,Stepanka Vlckova,Katerina Honkova,Jakub Ondracek,Irena Chvojkova,Daniela Pelclova,Vladimir Zdimal,Pavel Rossner,Jan Topinka,Lucie Lischkova

doi:10.3390/ijms22157834

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.

Highlights

The term “epigenetics”, already coined by the embryologist and developmental biologist Conrad Waddington in the year 1942 [1], was originally defined as “the branch of biology which studies the causal interactions between genes and their products which bring the phenotype into being” [2]
The selected participants involved in this study were recruited from subjects involved in our sampling performed for four consecutive years (2016–2019), as described in detail in the Materials and Methods section
The results show no differences in the DNA methylation pattern for the whole CpG array data set (Figure 1), which included more than 850,000 CpG loci per person/year

Summary

Introduction

The term “epigenetics”, already coined by the embryologist and developmental biologist Conrad Waddington in the year 1942 [1], was originally defined as “the branch of biology which studies the causal interactions between genes and their products which bring the phenotype into being” [2] In this millennium, “epigenetics”, including issues related to histone modification, DNA methylation, or miRNA expression, became a phenomenon in various fields of biomedical research. The results of this comparison (B lymphocyte cells, Th helper cells, Tc cytotoxic cells, monocytes, neutrophils, natural killer cells; each for years 2016–2019) show generally stable individual blood cell profiles throughout the years in both groups. The data show no significant differences, the results for Tc cytotoxic cells (CD8T) are consistently (in all years) on the borderline of significance

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Discussion

Conclusion