Nejvíce citovaný článek - PubMed ID 30103442
Markers of Oxidative Stress in the Exhaled Breath Condensate of Workers Handling Nanocomposites
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.
- Klíčová slova
- Occupational exposure, machining, nanoparticles, transcriptome changes, welding,
- MeSH
- dospělí MeSH
- inhalační expozice škodlivé účinky analýza MeSH
- lidé středního věku MeSH
- lidé MeSH
- messenger RNA genetika krev MeSH
- mikro RNA genetika krev MeSH
- nanočástice * škodlivé účinky MeSH
- pracovní expozice * škodlivé účinky analýza MeSH
- stanovení celkové genové exprese MeSH
- transkriptom * účinky léků MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- messenger RNA MeSH
- mikro RNA MeSH
OBJECTIVES: Nanotechnology is a fast-growing field in both science and industry. However, experimental studies brought warning data concerning the negative effect of engineered nanoparticle exposure leading to oxidative stress, inflammation, decreased immune cell viability, and genotoxicity. The consequences of human exposure may appear with decades of latency. Therefore, more data is needed to identify the hazardous effects of nanoparticles. Exposure should be under control and biomarkers of effect are urgently searched. METHODS: Exposures of researchers working with nanocomposites were measured in yearly intervals for 5 years and biomarkers of oxidative stress and/or antioxidant capacity were analysed. Exposure to aerosols with nanoparticles was measured repeatedly using online and offline instruments during both the machining of geopolymer samples with epoxide resin and nanoSiO2 filler and metal surface welding. The levels of biomarkers of oxidation of lipids, nucleic acids and proteins were analysed in exhaled breath condensate (EBC) of researchers and controls in 2016-2018. In 2019 and 2020, glutathione was measured in plasma to assess their antioxidant status. The trends in both exposure and EBC biomarkers' levels were analysed. RESULTS: On average, 21 researchers were examined yearly (aged 40 ± 5 years, exposure 14 ± 3 years). After 5 years, the mean mass concentration dropped from 0.921 to 0.563 mg/m3 and mean total number of particle concentrations from 146,106 to 17,621/cm3. The majority of biomarkers of oxidation of lipids, proteins and nucleic acids decreased (p < 0.05) during repeated measurements from the highest levels being mostly found in 2016. Glutathione in plasma in 2019-2020 was elevated (p < 0.01) as compared to controls. CONCLUSIONS: The adaptation of long-term exposed researchers may give a plausible explanation. However, to our meaning, the precautionary principle and higher attention of the employers to the potential risk of nanoparticles by reducing nanoparticles exposure by almost one order of magnitude played the key role.
- Klíčová slova
- adaptation, engineered nanoparticles, oxidative stress, prevention, spirometry,
- MeSH
- biologické markery analýza MeSH
- dospělí MeSH
- lidé MeSH
- nanočástice škodlivé účinky MeSH
- nanostruktury * škodlivé účinky MeSH
- oxidační stres MeSH
- pracovní expozice * prevence a kontrola analýza MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- biologické markery 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.
- Klíčová slova
- DNA methylation, epigenetics, human, microarrays, nanoparticles, occupational exposure, time changes,
- MeSH
- CpG ostrůvky MeSH
- dospělí MeSH
- epigeneze genetická * MeSH
- lidé středního věku MeSH
- lidé MeSH
- metylace DNA * MeSH
- nanočástice škodlivé účinky MeSH
- nemoci z povolání chemicky indukované epidemiologie genetika MeSH
- pracovní expozice škodlivé účinky MeSH
- regulace genové exprese účinky léků MeSH
- studie případů a kontrol MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika epidemiologie MeSH
Human data concerning exposure to nanoparticles are very limited, and biomarkers for monitoring exposure are urgently needed. In a follow-up of a 2016 study in a nanocomposites plant, in which only exhaled breath condensate (EBC) was examined, eight markers of oxidative stress were analyzed in three bodily fluids, i.e., EBC, plasma and urine, in both pre-shift and post-shift samples in 2017 and 2018. Aerosol exposures were monitored. Mass concentration in 2017 was 0.351 mg/m3 during machining, and 0.179 and 0.217 mg/m3 during machining and welding, respectively, in 2018. In number concentrations, nanoparticles formed 96%, 90% and 59%, respectively. In both years, pre-shift elevations of 50.0% in EBC, 37.5% in plasma and 6.25% in urine biomarkers were observed. Post-shift elevation reached 62.5% in EBC, 68.8% in plasma and 18.8% in urine samples. The same trend was observed in all biological fluids. Individual factors were responsible for the elevation of control subjects' afternoon vs. morning markers in 2018; all were significantly lower compared to those of workers. Malondialdehyde levels were always acutely shifted, and 8-hydroxy-2-deoxyguanosine levels best showed chronic exposure effect. EBC and plasma analysis appear to be the ideal fluids for bio-monitoring of oxidative stress arising from engineered nanomaterials. Potential late effects need to be targeted and prevented, as there is a similarity of EBC findings in patients with silicosis and asbestosis.
- Klíčová slova
- biomarkers, controls, exhaled breath condensate, nanoparticles, oxidative stress, plasma, urine, workers,
- Publikační typ
- časopisecké články MeSH
The risk of exposure to nanoparticles (NPs) has rapidly increased during the last decade due to the vast use of nanomaterials (NMs) in many areas of human life. Despite this fact, human biomonitoring studies focused on the effect of NP exposure on DNA alterations are still rare. Furthermore, there are virtually no epigenetic data available. In this study, we investigated global and gene-specific DNA methylation profiles in a group of 20 long-term (mean 14.5 years) exposed, nanocomposite, research workers and in 20 controls. Both groups were sampled twice/day (pre-shift and post-shift) in September 2018. We applied Infinium Methylation Assay, using the Infinium MethylationEPIC BeadChips with more than 850,000 CpG loci, for identification of the DNA methylation pattern in the studied groups. Aerosol exposure monitoring, including two nanosized fractions, was also performed as proof of acute NP exposure. The obtained array data showed significant differences in methylation between the exposed and control groups related to long-term exposure, specifically 341 CpG loci were hypomethylated and 364 hypermethylated. The most significant CpG differences were mainly detected in genes involved in lipid metabolism, the immune system, lung functions, signaling pathways, cancer development and xenobiotic detoxification. In contrast, short-term acute NP exposure was not accompanied by DNA methylation changes. In summary, long-term (years) exposure to NP is associated with DNA epigenetic alterations.
- Klíčová slova
- 850K microarray, CpG sites, DNA methylation, epigenetic adaptation, human, nanoparticles, occupational exposure,
- MeSH
- dospělí MeSH
- epigeneze genetická MeSH
- genom lidský MeSH
- lidé středního věku MeSH
- lidé MeSH
- metylace DNA účinky léků MeSH
- mladý dospělý MeSH
- nanočástice škodlivé účinky MeSH
- nanokompozity škodlivé účinky MeSH
- pracovní expozice * MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
The present pilot study tested the efficiency of nanoTiO2 sunscreen to prevent the oxidative stress/inflammation caused by ultraviolet (UV) radiation using biomarkers in subjects' blood, urine, and exhaled breath condensate (EBC). In addition, the skin absorption of nanoTiO2 was studied. Six identical subjects participated in three tests: (A) nanoTiO2 sunscreen, (B) UV radiation, and (C) sunscreen + UV. The first samples were collected before the test and the second after sunscreen application and/or UV exposure. On day 4, the third samples were collected, and the sunscreen was washed off, and the fourth samples were collected on day 11. The following biomarkers were measured: malondialdehyde, 4-hydroxy-trans-hexenal, 4-hydroxy-trans-nonenal, aldehydes C6-C12, 8-iso-Prostaglandin F2α, o-tyrosine, 3-chlorotyrosine, 3-nitrotyrosine, 8-hydroxy-2-deoxyguanosine, 8-hydroxyguanosine, 5-hydroxymethyl uracil, and leukotrienes, using liquid chromatography-electrospray ionisation-tandem mass spectrometry. Titania was measured using inductively coupled plasma mass spectrometry and TiO2 nanoparticles by transmission and scanning electron microscopy. Sunscreen alone did not elevate the markers, but UV increased the biomarkers in the plasma, urine, and EBC. The sunscreen prevented skin redness, however it did not inhibit the elevation of oxidative stress/inflammatory markers. Titania and nanoTiO2 particles were found in the plasma and urine (but not in the EBC) in all sunscreen users, suggesting their skin absorption.
Thousands of researchers and workers worldwide are employed in nanocomposites manufacturing, yet little is known about their respiratory health. Aerosol exposures were characterized using real time and integrated instruments. Aerosol mass concentration ranged from 0.120 mg/m³ to 1.840 mg/m³ during nanocomposite machining processes; median particle number concentration ranged from 4.8 × 10⁴ to 5.4 × 10⁵ particles/cm³. The proportion of nanoparticles varied by process from 40 to 95%. Twenty employees, working in nanocomposite materials research were examined pre-shift and post-shift using spirometry and fractional exhaled nitric oxide (FeNO) in parallel with 21 controls. Pro-inflammatory leukotrienes (LT) type B4, C4, D4, and E4; tumor necrosis factor (TNF); interleukins; and anti-inflammatory lipoxins (LXA4 and LXB4) were analyzed in their exhaled breath condensate (EBC). Chronic bronchitis was present in 20% of researchers, but not in controls. A significant decrease in forced expiratory volume in 1 s (FEV1) and FEV1/forced vital capacity (FVC) was found in researchers post-shift (p ˂ 0.05). Post-shift EBC samples were higher for TNF (p ˂ 0.001), LTB4 (p ˂ 0.001), and LTE4 (p ˂ 0.01) compared with controls. Nanocomposites production was associated with LTB4 (p ˂ 0.001), LTE4 (p ˂ 0.05), and TNF (p ˂ 0.001), in addition to pre-shift LTD4 and LXB4 (both p ˂ 0.05). Spirometry documented minor, but significant, post-shift lung impairment. TNF and LTB4 were the most robust markers of biological effects. Proper ventilation and respiratory protection are required during nanocomposites processing.
- Klíčová slova
- FeNO, exhaled breath condensate (EBC), inflammation, nanocomposites, nanoparticles, spirometry,
- Publikační typ
- časopisecké články MeSH
