AIM: To investigate the effect of acute (daily) inhalation of nanoparticles (NPs) on the transcriptomic profile of male nanocomposite research workers with a history of long-term exposure (years). MATERIALS & METHODS: Whole genome mRNA and miRNA expression changes were analyzed from blood samples collected before and after machining or welding. Exposure in the work environment was assessed using stationary and personal monitoring. RESULTS: Following PM0.1 exposure, a significant decrease in the expression of DDIT4 and FKBP5, genes involved in the stress response, was detected in exposed workers. In the Machining group, the DDIT4 expression correlated with the exposure dose. Increased levels of miR30-d-5p and miR-3613-5p (both involved in carcinogenesis) in welders were associated with the NP exposure dose, highlighting their potential suitability as inhalation exposure markers. CONCLUSION: The results from this pilot transcriptomic analysis (mRNA and miRNA) indicate that exposure to NPs contributes to immune system deregulation and alters the pathways related to cancer. Therefore, the use of protective equipment, as well as obtaining more data by additional research, is highly recommended.

This is a follow-up study to our previous research that examined the acute effects of occupational inhalation exposure to nanoparticles (NPs) in females without a previous exposure history. This time, we reexamined the impacts of acute exposure in a group of 18 male workers, including welders and nanocomposite machinists with a long-term previous exposure history at the transcriptomic level. Whole genome transcriptomics studies the complete set of RNA molecules, or transcripts, produced in a cell or organism at a specific time. The analysis allows us to understand which genes are active/inactive, how they are regulated, and how they contribute to various biological processes or diseases. We looked at changes in mRNA and miRNA (types of RNA) from blood samples taken before and after workers were exposed to dust and fumes during machining and welding. We also monitored the exposure doses. The results suggest that inhaled NPs may present an occupational hazard to human health. The transcriptomic analysis shows that exposure to welding fumes and nanocomposite dust from machining affects the immune system and alters cancer-related pathways. Our research helps to understand NP exposure effects and may contribute to minimizing the negative health consequences of their inhalation.

• Keywords
• Occupational exposure, machining, nanoparticles, transcriptome changes, welding,
• MeSH
• Adult MeSH
• Inhalation Exposure adverse effects   analysis   MeSH
• Middle Aged MeSH
• Humans MeSH
• RNA, Messenger genetics   blood   MeSH
• MicroRNAs genetics   blood   MeSH
• Nanoparticles * adverse effects   MeSH
• Occupational Exposure * adverse effects   analysis   MeSH
• Gene Expression Profiling MeSH
• Transcriptome * drug effects   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• RNA, Messenger MeSH
• MicroRNAs MeSH

The aim of the study was to analyze the variables that modify the levels of oxidative DNA damage and lipid peroxidation in non-smoking mothers and their newborns from environmentally distinct localities of the Czech Republic: Ceske Budejovice (CB, an agricultural region) and Karvina (an industrial region). Personal, socio-economic and medical data, concentrations of particulate matter of aerodynamic diameter < 2.5 µm (PM2.5) and benzo[a]pyrene (B[a]P) in the ambient air, the activities of antioxidant mechanisms (superoxide dismutase, catalase, glutathione peroxidase) and antioxidant capacity), the levels of pro-inflammatory cytokines, the concentrations of persistent organic pollutants (POPs) in blood plasma/cord blood plasma and urinary levels of polycyclic aromatic hydrocarbons metabolites (OH-PAHs) were investigated as parameters potentially affecting the markers of DNA oxidation (8-oxo-7,8-dihydro-2'-deoxyguanosine, 8-oxodG) and lipid peroxidation (15-F2t-isoprostane, 15-F2t-IsoP). Significantly higher levels of POPs were detected in the plasma of mothers/newborns from CB (p < 0.001), while increased external levels of B[a]P and PM2.5, confirmed by analyzing urinary OH-PAHs, were found in Karvina subjects (p < 0.001). In mothers, multivariate analysis showed no significant difference in oxidative stress markers (15-F2t-IsoP, 8-oxodG) between the two localities. The analysis further revealed that neither in CB nor, unexpectedly, in Karvina, did PAH exposure affect maternal lipid peroxidation. Significant associations between OH-PAHs and 15-F2t-IsoP or 8-oxodG were observed only in newborns. In addition, multivariate analyses revealed a borderline significant association between locality and 8-oxodG in the urine of all newborns (p = 0.05). In conclusion, not only the maternal exposure of PAHs but also some POPs can negatively affect oxidative stress status in the early-life of newborns.

• Keywords
• antioxidant response and inflammatory cytokines, environmental pollution, lipid peroxidation, maternal exposure to newborn, oxidative DNA damage,
• Publication type
• Journal Article MeSH

DNA methylation is the most studied epigenetic mechanism that regulates gene expression, and it can serve as a useful biomarker of prior environmental exposure and future health outcomes. This study focused on DNA methylation profiles in a human cohort, comprising 125 nonsmoking city policemen (sampled twice), living and working in three localities (Prague, Ostrava and Ceske Budejovice) of the Czech Republic, who spent the majority of their working time outdoors. The main characterization of the localities, differing by major sources of air pollution, was defined by the stationary air pollution monitoring of PM2.5, B[a]P and NO2. DNA methylation was analyzed by a genome-wide microarray method. No season-specific DNA methylation pattern was discovered; however, we identified 13,643 differentially methylated CpG loci (DML) for a comparison between the Prague and Ostrava groups. The most significant DML was cg10123377 (log2FC = -1.92, p = 8.30 × 10-4) and loci annotated to RPTOR (total 20 CpG loci). We also found two hypomethylated loci annotated to the DNA repair gene XRCC5. Groups of DML annotated to the same gene were linked to diabetes mellitus (KCNQ1), respiratory diseases (PTPRN2), the dopaminergic system of the brain and neurodegenerative diseases (NR4A2). The most significant possibly affected pathway was Axon guidance, with 86 potentially deregulated genes near DML. The cluster of gene sets that could be affected by DNA methylation in the Ostrava groups mainly includes the neuronal functions and biological processes of cell junctions and adhesion assembly. The study demonstrates that the differences in the type of air pollution between localities can affect a unique change in DNA methylation profiles across the human genome.

• Keywords
• DNA methylation, air pollution, environment, epigenetics, molecular epidemiology,
• MeSH
• Genome-Wide Association Study MeSH
• Adult MeSH
• Air Pollutants adverse effects   MeSH
• Middle Aged MeSH
• Humans MeSH
• DNA Methylation drug effects   MeSH
• Police * MeSH
• Environmental Exposure adverse effects   MeSH
• Air Pollution adverse effects   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Czech Republic MeSH
• Names of Substances
• Air Pollutants MeSH

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.

• Keywords
• DNA methylation, epigenetics, human, microarrays, nanoparticles, occupational exposure, time changes,
• MeSH
• CpG Islands MeSH
• Adult MeSH
• Epigenesis, Genetic * MeSH
• Middle Aged MeSH
• Humans MeSH
• DNA Methylation * MeSH
• Nanoparticles adverse effects   MeSH
• Occupational Diseases chemically induced   epidemiology   genetics   MeSH
• Occupational Exposure adverse effects   MeSH
• Gene Expression Regulation drug effects   MeSH
• Case-Control Studies MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Czech Republic epidemiology   MeSH

Small non-coding RNA molecules (miRNAs) play an important role in the epigenetic regulation of gene expression. As these molecules have been repeatedly implicated in human cancers, they have been suggested as biomarkers of the disease. Additionally, miRNA levels have been shown to be affected by environmental pollutants, including airborne contaminants. In this review, we searched the current literature for miRNAs involved in lung cancer, as well as miRNAs deregulated as a result of exposure to air pollutants. We then performed a synthesis of the data and identified those molecules commonly deregulated under both conditions. We detected a total of 25 miRNAs meeting the criteria, among them, miR-222, miR-21, miR-126-3p, miR-155 and miR-425 being the most prominent. We propose these miRNAs as biomarkers of choice for the identification of human populations exposed to air pollution with a significant risk of developing lung cancer.

• Keywords
• air pollution, biomarker, exposure, human, lung cancer, miRNA,
• Publication type
• Journal Article MeSH
• Review MeSH