Publications by authors named "Andrea Rossnerova"

48 Publications

The Impact of Air Pollution Exposure on the MicroRNA Machinery and Lung Cancer Development.

J Pers Med 2021 Jan 19;11(1). Epub 2021 Jan 19.

Department of Nanotoxicology and Molecular Epidemiology, Institute of Experimental Medicine CAS, Videnska 1083, 142 20 Prague, Czech Republic.

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.
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http://dx.doi.org/10.3390/jpm11010060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833364PMC
January 2021

Ordinary Gasoline Emissions Induce a Toxic Response in Bronchial Cells Grown at Air-Liquid Interface.

Int J Mol Sci 2020 Dec 23;22(1). Epub 2020 Dec 23.

Department of Nanotoxicology and Molecular Epidemiology, Institute of Experimental Medicine of the CAS, Videnska 1083, 142 20 Prague, Czech Republic.

Gasoline engine emissions have been classified as possibly carcinogenic to humans and represent a significant health risk. In this study, we used MucilAir™, a three-dimensional (3D) model of the human airway, and BEAS-2B, cells originating from the human bronchial epithelium, grown at the air-liquid interface to assess the toxicity of ordinary gasoline exhaust produced by a direct injection spark ignition engine. The transepithelial electrical resistance (TEER), production of mucin, and lactate dehydrogenase (LDH) and adenylate kinase (AK) activities were analyzed after one day and five days of exposure. The induction of double-stranded DNA breaks was measured by the detection of histone H2AX phosphorylation. Next-generation sequencing was used to analyze the modulation of expression of the relevant 370 genes. The exposure to gasoline emissions affected the integrity, as well as LDH and AK leakage in the 3D model, particularly after longer exposure periods. Mucin production was mostly decreased with the exception of longer BEAS-2B treatment, for which a significant increase was detected. DNA damage was detected after five days of exposure in the 3D model, but not in BEAS-2B cells. The expression of and was modulated in MucilAir™ tissues after 5 days of treatment. In BEAS-2B cells, the expression of 39 mRNAs was affected after short exposure, most of them were upregulated. The five days of exposure modulated the expression of 11 genes in this cell line. In conclusion, the ordinary gasoline emissions induced a toxic response in MucilAir™. In BEAS-2B cells, the biological response was less pronounced, mostly limited to gene expression changes.
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http://dx.doi.org/10.3390/ijms22010079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801947PMC
December 2020

Telomere length in peripheral blood lymphocytes related to genetic variation in telomerase, prognosis and clinicopathological features in breast cancer patients.

Mutagenesis 2020 12;35(6):491-497

Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Videnska, Prague, Czech Republic.

Disruption of telomere length (TL) homeostasis in peripheral blood lymphocytes has been previously assessed as a potential biomarker of breast cancer (BC) risk. The present study addressed the relationship between lymphocyte TL (LTL), prognosis and clinicopathological features in the BC patients since these associations are insufficiently explored at present. LTL was measured in 611 BC patients and 154 healthy controls using the monochrome multiplex quantitative Polymerase Chain Reaction assay. In addition, we genotyped nine TL-associated single-nucleotide polymorphisms that had been identified through genome-wide association studies. Our results showed that the patients had significantly (P = 0.001, Mann-Whitney U-test) longer LTL [median (interquartile range); 1.48 (1.22-1.78)] than the healthy controls [1.27 (0.97-1.82)]. Patients homozygous (CC) for the common allele of hTERT rs2736108 or the variant allele (CC) of hTERC rs16847897 had longer LTL. The latter association remained statistically significant in the recessive genetic model after the Bonferroni correction (P = 0.004, Wilcoxon two-sample test). We observed no association between LTL and overall survival or relapse-free survival of the patients. LTL did not correlate with cancer staging based on Union for International Cancer Control (UICC), The tumor node metastasis (TNM) staging system classification, tumour grade or molecular BC subtypes. Overall, we observed an association between long LTL and BC disease and an association of the hTERC rs16847897 CC genotype with increased LTL. However, no association between LTL, clinicopathological features and survival of the patients was found.
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http://dx.doi.org/10.1093/mutage/geaa030DOI Listing
December 2020

Three-Year Study of Markers of Oxidative Stress in Exhaled Breath Condensate in Workers Producing Nanocomposites, Extended by Plasma and Urine Analysis in Last Two Years.

Nanomaterials (Basel) 2020 Dec 6;10(12). Epub 2020 Dec 6.

J. Heyrovský Institute of Physical Chemistry CAS, Dolejškova 3, 182 23 Prague 8, Czech Republic.

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/m during machining, and 0.179 and 0.217 mg/m 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.
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http://dx.doi.org/10.3390/nano10122440DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762143PMC
December 2020

The Impact of Cesarean and Vaginal Delivery on Results of Psychological Cognitive Test in 5 Year Old Children.

Medicina (Kaunas) 2020 Oct 21;56(10). Epub 2020 Oct 21.

Faculty of Health and Social Sciences, University of South Bohemia, 370 05 Ceske Budejovice, Czech Republic.

The impact of cesarean and vaginal delivery on cognitive development was analyzed in 5 year old children. : Two cohorts of 5 year old children born in the years 2013 and 2014 in Karvina (Northern Moravia) and Ceske Budejovice (Southern Bohemia) were studied for their cognitive development related to vaginal ( = 117) and cesarean types of delivery ( = 51). The Bender Visual Motor Gestalt Test (BG test) and the Raven Colored Progressive Matrices (RCPM test) were used as psychological tests. : In the comparison of vaginal delivery vs. cesarean section, the children delivered by cesarean section scored lower and, therefore, achieved poorer performance in cognitive tests compared to those born by vaginal delivery, as shown in the RCPM ( < 0.001) and in the BG test ( < 0.001). When mothers' education level was considered, the children whose mothers achieved a university degree scored higher in both the RCPM test ( < 0.001) and the BG test ( < 0.01) compared to the children of mothers with lower secondary education. When comparing mothers with a university degree to those with higher secondary education, there was a significant correlation between level of education and score achieved in the RCPM test ( < 0.001), but not in the BG test. : According to our findings, the mode of delivery seems to have a significant influence on performance in psychological cognitive tests in 5 year old children in favor of those who were born by vaginal delivery. Since cesarean-born children scored notably below vaginally born children, it appears possible that cesarean delivery may have a convincingly adverse effect on children's further cognitive development.
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http://dx.doi.org/10.3390/medicina56100554DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7589839PMC
October 2020

The Molecular Mechanisms of Adaptive Response Related to Environmental Stress.

Int J Mol Sci 2020 Sep 25;21(19). Epub 2020 Sep 25.

Department of Nanotoxicology and Molecular Epidemiology, Institute of Experimental Medicine, 14220 Prague, Czech Republic.

The exposure of living organisms to environmental stress triggers defensive responses resulting in the activation of protective processes. Whenever the exposure occurs at low doses, defensive effects overwhelm the adverse effects of the exposure; this adaptive situation is referred to as "hormesis". Environmental, physical, and nutritional hormetins lead to the stimulation and strengthening of the maintenance and repair systems in cells and tissues. Exercise, heat, and irradiation are examples of physical hormetins, which activate heat shock-, DNA repair-, and anti-oxidative-stress responses. The health promoting effect of many bio-actives in fruits and vegetables can be seen as the effect of mildly toxic compounds triggering this adaptive stimulus. Numerous studies indicate that living organisms possess the ability to adapt to adverse environmental conditions, as exemplified by the fact that DNA damage and gene expression profiling in populations living in the environment with high levels of air pollution do not correspond to the concentrations of pollutants. The molecular mechanisms of the hormetic response include modulation of (a) transcription factor Nrf2 activating the synthesis of glutathione and the subsequent protection of the cell; (b) DNA methylation; and (c) microRNA. These findings provide evidence that hormesis is a toxicological event, occurring at low exposure doses to environmental stressors, having the benefit for the maintenance of a healthy status.
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http://dx.doi.org/10.3390/ijms21197053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7582272PMC
September 2020

The genotoxic effects in the leukocytes of workers handling nanocomposite materials.

Mutagenesis 2020 09;35(4):331-340

Department of Nanotoxicology and Molecular Epidemiology, Institute of Experimental Medicine of the Czech Academy of Sciences, Videnska, Prague, Czech Republic.

The extensive development of nanotechnologies and nanomaterials poses a number of questions to toxicologists about the potential health risks of exposure to nanoparticles (NP). In this study, we analysed DNA damage in the leukocytes of 20 workers who were long-term exposed (18 ± 10 years) to NP in their working environment. Blood samples were collected in September 2016, before and after a shift, to assess (i) the chronic effects of NP on DNA (pre-shift samples) and (ii) the acute effects of exposure during the shift (the difference between pre- and post-shift samples). The samples from matched controls were taken in parallel with workers before the shift. Leukocytes were isolated from heparinised blood on a Ficoll gradient. The enzyme-modified comet assay (DNA formamido-pyrimidine-glycosylase and endonuclease III) demonstrated a considerable increase of both single- and double-strand breaks in DNA (DNA-SB) and oxidised bases when compared with the controls (2.4× and 2×, respectively). Acute exposure induced a further increase of DNA-SB. The welding and smelting of nanocomposites represented a higher genotoxic risk than milling and grinding of nanocomposite surfaces. Obesity appeared to be a factor contributing to an increased risk of oxidative damage to DNA. The data also indicated a higher susceptibility of males vs. females to NP exposure. The study was repeated in September 2017. The results exhibited similar trend, but the levels of DNA damage in the exposed subjects were lower compared to previous year. This was probably associated with lower exposure to NP in consequence of changes in nanomaterial composition and working operations. The further study involving also monitoring of personal exposures to NP is necessary to identify (i) the main aerosol components responsible for genotoxic effects in workers handling nanocomposites and (ii) the primary cause of gender differences in response to NP action.
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http://dx.doi.org/10.1093/mutage/geaa016DOI Listing
September 2020

The Differential Effect of Carbon Dots on Gene Expression and DNA Methylation of Human Embryonic Lung Fibroblasts as a Function of Surface Charge and Dose.

Int J Mol Sci 2020 Jul 4;21(13). Epub 2020 Jul 4.

Department of Nanotoxicology and Molecular Epidemiology, Institute of Experimental Medicine of the Czech Academy of Sciences, 14220 Prague, Czech Republic.

This study presents a toxicological evaluation of two types of carbon dots (CD), similar in size (<10 nm) but differing in surface charge. Whole-genome mRNA and miRNA expression (RNAseq), as well as gene-specific DNA methylation changes, were analyzed in human embryonic lung fibroblasts (HEL 12469) after 4 h and 24 h exposure to concentrations of 10 and 50 µg/mL (for positive charged CD; pCD) or 10 and 100 µg/mL (for negative charged CD, nCD). The results showed a distinct response for the tested nanomaterials (NMs). The exposure to pCD induced the expression of a substantially lower number of mRNAs than those to nCD, with few commonly differentially expressed genes between the two CDs. For both CDs, the number of deregulated mRNAs increased with the dose and exposure time. The pathway analysis revealed a deregulation of processes associated with immune response, tumorigenesis and cell cycle regulation, after exposure to pCD. For nCD treatment, pathways relating to cell proliferation, apoptosis, oxidative stress, gene expression, and cycle regulation were detected. The expression of miRNAs followed a similar pattern: more pronounced changes after nCD exposure and few commonly differentially expressed miRNAs between the two CDs. For both CDs the pathway analysis based on miRNA-mRNA interactions, showed a deregulation of cancer-related pathways, immune processes and processes involved in extracellular matrix interactions. DNA methylation was not affected by exposure to any of the two CDs. In summary, although the tested CDs induced distinct responses on the level of mRNA and miRNA expression, pathway analyses revealed a potential common biological impact of both NMs independent of their surface charge.
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http://dx.doi.org/10.3390/ijms21134763DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7369946PMC
July 2020

Genotoxicant exposure, activation of the aryl hydrocarbon receptor, and lipid peroxidation in cultured human alveolar type II A549 cells.

Mutat Res 2020 05 6;853:503173. Epub 2020 Apr 6.

Department of Genetic Toxicology and Nanotoxicology, Institute of Experimental Medicine of the CAS, Videnska 1083, 142 20, Prague, Czech Republic. Electronic address:

The aryl hydrocarbon receptor (AhR) transcription factor is activated by polycyclic aromatic hydrocarbons (PAH) and other ligands. Activated AhR binds to dioxin responsive elements (DRE) and initiates transcription of target genes, including the gene encoding prostaglandin endoperoxide synthase 2 (PTGS-2), which is also activated by the transcription factor NF-ĸB. PTGS-2 catalyzes the conversion of arachidonic acid (AA) into prostaglandins, thromboxanes or isoprostanes. 15-F2t-Isoprostane (IsoP), regarded as a universal marker of lipid peroxidation, is also induced by PAH exposure. We investigated the processes associated with lipid peroxidation in human alveolar basal epithelial cells (A549) exposed for 4 h or 24 h to model PAH (benzo[a]pyrene, BaP; 3-nitrobenzanthrone, 3-NBA) and organic extracts from ambient air particulate matter (EOM), collected in two seasons in a polluted locality. Both EOM induced the expression of CYP1A1 and CYP1B1; 24 h treatment significantly reduced PTGS-2 expression. IsoP levels decreased after both exposure periods, while the concentration of AA was not affected. The effects induced by BaP were similar to EOM except for increased IsoP levels after 4 h exposure and elevated AA concentration after 24 h treatment. In contrast, 3-NBA treatment did not induce CYP expression, had a weak effect on PTGS-2 expression, and, similar to BaP, induced IsoP levels after 4 h exposure and AA levels after 24 h treatment. All tested compounds induced the activity of NF-ĸB after the longer exposure period. In summary, our data suggest that EOM, and partly BaP, reduce lipid peroxidation by a mechanism that involves AhR-dependent inhibition of PTGS-2 expression. The effect of 3-NBA on IsoP levels is probably mediated by a different mechanism independent of AhR activation.
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http://dx.doi.org/10.1016/j.mrgentox.2020.503173DOI Listing
May 2020

DNA Methylation Profiles in a Group of Workers Occupationally Exposed to Nanoparticles.

Int J Mol Sci 2020 Mar 31;21(7). Epub 2020 Mar 31.

Department of Machining and Assembly, Department of Engineering Technology, Department of Material Science, Faculty of Mechanical Engineering, Technical University in Liberec, Studentska 1402/2 Liberec, Czech Republic.

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.
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http://dx.doi.org/10.3390/ijms21072420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7177382PMC
March 2020

Gene Expression and Epigenetic Changes in Mice Following Inhalation of Copper(II) Oxide Nanoparticles.

Nanomaterials (Basel) 2020 Mar 18;10(3). Epub 2020 Mar 18.

Department of Genetic Toxicology and Epigenetics, Institute of Experimental Medicine of the Czech Academy of Sciences, 14220 Prague, Czech Republic.

We investigated the transcriptomic response and epigenetic changes in the lungs of mice exposed to inhalation of copper(II) oxide nanoparticles (CuO NPs) (8 × 10 NPs/m) for periods of 3 days, 2 weeks, 6 weeks, and 3 months. A whole genome transcriptome and miRNA analysis was performed using next generation sequencing. Global DNA methylation was assessed by ELISA. The inhalation resulted in the deregulation of mRNA transcripts: we detected 170, 590, 534, and 1551 differentially expressed transcripts after 3 days, 2 weeks, 6 weeks, and 3 months of inhalation, respectively. Biological processes and pathways affected by inhalation, differed between 3 days exposure (collagen formation) and longer treatments (immune response). Periods of two weeks exposure further induced apoptotic processes, 6 weeks of inhalation affected the cell cycle, and 3 months of treatment impacted the processes related to cell adhesion. The expression of miRNA was not affected by 3 days of inhalation. Prolonged exposure periods modified miRNA levels, although the numbers were relatively low (17, 18, and 38 miRNAs, for periods of 2 weeks, 6 weeks, and 3 months, respectively). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis based on miRNA-mRNA interactions, revealed the deregulation of processes implicated in the immune response and carcinogenesis. Global DNA methylation was not significantly affected in any of the exposure periods. In summary, the inhalation of CuO NPs impacted on both mRNA and miRNA expression. A significant transcriptomic response was already observed after 3 days of exposure. The affected biological processes and pathways indicated the negative impacts on the immune system and potential role in carcinogenesis.
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http://dx.doi.org/10.3390/nano10030550DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7153614PMC
March 2020

The Biological Effects of Complete Gasoline Engine Emissions Exposure in a 3D Human Airway Model (MucilAir) and in Human Bronchial Epithelial Cells (BEAS-2B).

Int J Mol Sci 2019 Nov 14;20(22). Epub 2019 Nov 14.

Department of Genetic Toxicology and Nanotoxicology, Institute of Experimental Medicine of the CAS, Videnska 1083, 142 20 Prague, Czech Republic.

The biological effects induced by complete engine emissions in a 3D model of the human airway (MucilAir) and in human bronchial epithelial cells (BEAS-2B) grown at the air-liquid interface were compared. The cells were exposed for one or five days to emissions generated by a Euro 5 direct injection spark ignition engine. The general condition of the cells was assessed by the measurement of transepithelial electrical resistance and mucin production. The cytotoxic effects were evaluated by adenylate kinase (AK) and lactate dehydrogenase (LDH) activity. Phosphorylation of histone H2AX was used to detect double-stranded DNA breaks. The expression of the selected 370 relevant genes was analyzed using next-generation sequencing. The exposure had minimal effects on integrity and AK leakage in both cell models. LDH activity and mucin production in BEAS-2B cells significantly increased after longer exposures; DNA breaks were also detected. The exposure affected and expression in MucilAir. There were no effects of this kind observed in BEAS-2B cells; in this system gene expression was rather affected by the time of treatment. The type of cell model was the most important factor modulating gene expression. In summary, the biological effects of complete emissions exposure were weak. In the specific conditions used in this study, the effects observed in BEAS-2B cells were induced by the exposure protocol rather than by emissions and thus this cell line seems to be less suitable for analyses of longer treatment than the 3D model.
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http://dx.doi.org/10.3390/ijms20225710DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6888625PMC
November 2019

Corrigendum to "Benzo[a]pyrene is associated with dysregulated myelo-lymphoid hematopoiesis in asthmatic children" [Environ. Int. 128 (2019) 218-232].

Environ Int 2019 Nov 28;132:105121. Epub 2019 Aug 28.

Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address:

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http://dx.doi.org/10.1016/j.envint.2019.105121DOI Listing
November 2019

Short-term and Long-term Exposure of the MucilAir™ Model to Polycyclic Aromatic Hydrocarbons.

Altern Lab Anim 2019 Mar 30;47(1):9-18. Epub 2019 Apr 30.

1 Department of Genetic Toxicology and Nanotoxicology, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic.

Cells grown in monocultures are widely used to model lung tissue. As a result of these culture conditions, these cells exhibit poor morphological similarity to those present in lung tissue. MucilAir™, a 3-D model comprising human basal, goblet and ciliated cells, represents a fully differentiated respiratory epithelium that can be used as an alternative and a more realistic system. The aim of our study was to compare the effects of short-term and long-term exposure to two polycyclic aromatic hydrocarbons (PAHs) - benzo[a]pyrene (B[a]P) and 3-nitrobenzanthrone (3-NBA) - using MucilAir as a model of human lung tissue. Two concentrations (0.1 μM and 1 μM) were tested at three time points (24 hours, 7 days and 28 days). Several aspects were assessed: cytotoxicity (lactate dehydrogenase (LDH) release), integrity of the cell layer (transepithelial electrical resistance (TEER)), induction of oxidative stress (reactive oxygen species production) and changes in the expression of selected genes involved in PAH metabolism ( and ) and the antioxidant response (, , , , and ). The results showed that exposure to B[a]P caused a spike in LDH release at day 5. Exposure to 3-NBA caused a number of spikes in LDH release, starting at day 5, and a decrease in TEER after 11 days. gene expression was upregulated after the 7-day and 28-day B[a]P exposures, as well as after the 24-hour and 7-day 3-NBA exposures. and were downregulated after both 24-hour PAH treatments. was upregulated after a 1-week exposure to 3-NBA. There were no significant changes in the messenger RNA (mRNA) levels of or . These results illustrate the potential use of this 3-D lung tissue model in studying the effects of chronic exposure to PAHs.
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http://dx.doi.org/10.1177/0261192919841484DOI Listing
March 2019

The repeated cytogenetic analysis of subjects occupationally exposed to nanoparticles: a pilot study.

Mutagenesis 2019 09;34(3):253-263

Department of Machining and Assembly, Technical University in Liberec, Liberec, Czech Republic.

The application of nanomaterials has been rapidly increasing during recent years. Inhalation exposure to nanoparticles (NP) may result in negative toxic effects but there is a critical lack of human studies, especially those related to possible DNA alterations. We analyzed pre-shift and post-shift a group of nanocomposite researchers with a long-term working background (17.8 ± 10.0 years) and matched controls. The study group consisted of 73.2% males and 26.8% females. Aerosol exposure monitoring during a working shift (involving welding, smelting, machining) to assess the differences in exposure to particulate matter (PM) including nanosized fractions <25-100 nm, and their chemical analysis, was carried out. A micronucleus assay using Human Pan Centromeric probes, was applied to distinguish between the frequency of centromere positive (CEN+) and centromere negative (CEN-) micronuclei (MN) in the binucleated cells. This approach allowed recognition of the types of chromosomal damage: losses and breaks. The monitoring data revealed differences in the exposure to NP related to individual working processes, and in the chemical composition of nanofraction. The cytogenetic results of this pilot study demonstrated a lack of effect of long-term (years) exposure to NP (total frequency of MN, P = 0.743), although this exposure may be responsible for DNA damage pattern changes (12% increase of chromosomal breaks-clastogenic effect). Moreover, short-term (daily shift) exposure could be a reason for the increase of chromosomal breaks in a subgroup of researchers involved in welding and smelting processes (clastogenic effect, P = 0.037). The gender and/or gender ratio of the study participants was also an important factor for the interpretation of the results. As this type of human study is unique, further research is needed to understand the effects of long-term and short-term exposure to NP.
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http://dx.doi.org/10.1093/mutage/gez016DOI Listing
September 2019

The processes associated with lipid peroxidation in human embryonic lung fibroblasts, treated with polycyclic aromatic hydrocarbons and organic extract from particulate matter.

Mutagenesis 2019 05;34(2):153-164

Department of Genetic Toxicology and Nanotoxicology, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic.

Polycyclic aromatic hydrocarbons (PAHs) may cause lipid peroxidation via reactive oxygen species generation. 15-F2t-isoprostane (IsoP), an oxidative stress marker, is formed from arachidonic acid (AA) by a free-radical induced oxidation. AA may also be converted to prostaglandins (PG) by prostaglandin-endoperoxide synthase (PTGS) induced by NF-κB. We treated human embryonic lung fibroblasts (HEL12469) with benzo[a]pyrene (B[a]P), 3-nitrobenzanthrone (3-NBA) and extractable organic matter (EOM) from ambient air particulate matter <2.5 µm for 4 and 24 h. B[a]P and 3-NBA induced expression of PAH metabolising, but not antioxidant enzymes. The concentrations of IsoP decreased, whereas the levels of AA tended to increase. Although the activity of NF-κB was not detected, the tested compounds affected the expression of prostaglandin-endoperoxide synthase 2 (PTGS2). The levels of prostaglandin E2 (PGE2) decreased following exposure to B[a]P, whereas 3-NBA exposure tended to increase PGE2 concentration. A distinct response was observed after EOM exposure: expression of PAH-metabolising enzymes was induced, IsoP levels increased after 24-h treatment but AA concentration was not affected. The activity of NF-κB increased after both exposure periods, and a significant induction of PTGS2 expression was found following 4-h treatment. Similarly to PAHs, the EOM exposure was associated with a decrease of PGE2 levels. In summary, exposure to PAHs with low pro-oxidant potential results in a decrease of IsoP levels implying 'antioxidant' properties. For such compounds, IsoP may not be a suitable marker of lipid peroxidation.
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http://dx.doi.org/10.1093/mutage/gez004DOI Listing
May 2019

Inhalation of ZnO Nanoparticles: Splice Junction Expression and Alternative Splicing in Mice.

Toxicol Sci 2019 03;168(1):190-200

*Department of Genetic Toxicology and Nanotoxicology, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague 14220, Czech Republic.

Despite the wide application of nanomaterials, toxicity studies of nanoparticles (NP) are often limited to in vitro cell models, and the biological impact of NP exposure in mammals has not been thoroughly investigated. Zinc oxide (ZnO) NPs are commonly used in various consumer products. To evaluate the effects of the inhalation of ZnO NP in mice, we studied splice junction expression in the lungs as a proxy to gene expression changes analysis. Female ICR mice were treated with 6.46 × 104 and 1.93 × 106 NP/cm3 for 3 days and 3 months, respectively. An analysis of differential expression and alternative splicing events in 298 targets (splice junctions) of 68 genes involved in the processes relevant to the biological effects of ZnO NP was conducted using next-generation sequencing. Three days of exposure resulted in the upregulation of IL-6 and downregulation of BID, GSR, NF-kB2, PTGS2, SLC11A2, and TXNRD1 splice junction expression; 3 months of exposure increased the expression of splice junctions in ALDH3A1, APAF1, BID, CASP3, DHCR7, GCLC, GCLM, GSR, GSS, EHHADH, FAS, HMOX-1, IFNγ, NF-kB1, NQO-1, PTGS1, PTGS2, RAD51, RIPK2, SRXN1, TRAF6, and TXNRD1. Alternative splicing of TRAF6 and TXNRD1 was induced after 3 days of exposure to 1.93 × 106 NP/cm3. In summary, we observed changes of splice junction expression in genes involved in oxidative stress, apoptosis, immune response, inflammation, and DNA repair, as well as the induction of alternative splicing in genes associated with oxidative stress and inflammation. Our data indicate the potential negative biological effects of ZnO NP inhalation.
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http://dx.doi.org/10.1093/toxsci/kfy288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6390655PMC
March 2019

Gene expression profiling in healthy newborns from diverse localities of the Czech Republic.

Environ Mol Mutagen 2018 06 30;59(5):401-415. Epub 2018 Mar 30.

Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic.

Prenatal exposure to air pollution is associated with intrauterine growth restriction and low birth weight. Gene expression changes in newborns in relation to air pollution have not been sufficiently studied. We analyzed whole genome expression in cord blood leukocytes of 202 newborns from diverse localities of the Czech Republic, differing among other factors in levels of air pollution: the district of Karvina (characterized by higher concentration of air pollutants) and Ceske Budejovice (lower air pollution levels). We aimed to identify differentially expressed genes (DEGs) and pathways in relation to locality and concentration of air pollutants. We applied the linear model to identify the specific DEGs and the correlation analysis, to investigate the relationship between the concentrations of air pollutants and gene expression data. An analysis of biochemical pathways and gene set enrichment was also performed. In general, we observed modest changes of gene expression, mostly attributed to the effect of the locality. The highest number of DEGs was found in samples from the district of Karvina. A pathway analysis revealed a deregulation of processes associated with cell growth, apoptosis or cellular homeostasis, immune response-related processes or oxidative stress response. The association between concentrations of air pollutants and gene expression changes was weak, particularly for samples collected in Karvina. In summary, as we did not find a direct effect of exposure to air pollutants, we assume that the general differences in the environment, rather than actual concentrations of individual pollutants, represent a key factor affecting gene expression changes at delivery. Environ. Mol. Mutagen. 59:401-415, 2018. © 2018 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/em.22184DOI Listing
June 2018

Kinetics of ROS generation induced by polycyclic aromatic hydrocarbons and organic extracts from ambient air particulate matter in model human lung cell lines.

Mutat Res Genet Toxicol Environ Mutagen 2018 Mar 31;827:50-58. Epub 2018 Jan 31.

Department of Genetic Toxicology and Nanotoxicology, Institute of Experimental Medicine CAS, Prague, 14220, Czech Republic. Electronic address:

Polycyclic aromatic hydrocarbons (PAHs) associated with particulate matter (PM) may induce oxidative damage via reactive oxygen species (ROS) generation. However, the kinetics of ROS production and the link with antioxidant response induction has not been well studied. To elucidate the differences in oxidative potential of individual PAH compounds and extractable organic matter (EOM) from PM containing various PAH mixtures, we studied ROS formation and antioxidant response [total antioxidant capacity (TAC) and expression of HMOX1 and TXNRD1] in human alveolar basal epithelial cells (A549 cells) and human embryonic lung fibroblasts (HEL12469 cells). We treated the cells with three concentrations of model PAHs (benzo[a]pyrene, B[a]P; 3-nitrobenzanthrone, 3-NBA) and EOM from PM <2.5 μm (PM2.5). ROS levels were evaluated at 8 time intervals (30 min-24 h). In both cell lines, B[a]P treatment was associated with a time-dependent decrease of ROS levels. This trend was more pronounced in HEL12469 cells and was accompanied by increased TAC. A similar response was observed upon 3-NBA treatment in HEL12469 cells. In A549 cells, however, this compound significantly increased superoxide levels. This response was accompanied by the decrease of TAC as well as HMOX1 and TXNRD1 expression. In both cell lines, a short-time exposure to EOMs tended to increase ROS levels, while a marked decrease was observed after longer treatment periods. This was accompanied by the induction of HMOX1 and TXNRD1 expression in HEL12469 cells and increased TAC in A549 cells. In summary, our data indicate that in the studied cell lines B[a]P and EOMs caused a time-dependent decrease of intracellular ROS levels, probably due to the activation of the antioxidant response. This response was not detected in A549 cells following 3-NBA treatment, which acted as a strong superoxide inducer. Pro-oxidant properties of EOMs are limited to short-time exposure periods.
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http://dx.doi.org/10.1016/j.mrgentox.2018.01.006DOI Listing
March 2018

Adaptation of the human population to the environment: Current knowledge, clues from Czech cytogenetic and "omics" biomonitoring studies and possible mechanisms.

Mutat Res 2017 07 12;773:188-203. Epub 2017 Jul 12.

Department of Genetic Toxicology and Nanotoxicology, Institute of Experimental Medicine, Czech Academy of Sciences, 14220 Prague 4, Czech Republic. Electronic address:

The human population is continually exposed to numerous harmful environmental stressors, causing negative health effects and/or deregulation of biomarker levels. However, studies reporting no or even positive impacts of some stressors on humans are also sometimes published. The main aim of this review is to provide a comprehensive overview of the last decade of Czech biomonitoring research, concerning the effect of various levels of air pollution (benzo[a]pyrene) and radiation (uranium, X-ray examination and natural radon background), on the differently exposed population groups. Because some results obtained from cytogenetic studies were opposite than hypothesized, we have searched for a meaningful interpretation in genomic/epigenetic studies. A detailed analysis of our data supported by the studies of others and current epigenetic knowledge, leads to a hypothesis of the versatile mechanism of adaptation to environmental stressors via DNA methylation settings which may even originate in prenatal development, and help to reduce the resulting DNA damage levels. This hypothesis is fully in agreement with unexpected data from our studies (e.g. lower levels of DNA damage in subjects from highly polluted regions than in controls or in subjects exposed repeatedly to a pollutant than in those without previous exposure), and is also supported by differences in DNA methylation patterns in groups from regions with various levels of pollution. In light of the adaptation hypothesis, the following points may be suggested for future research: (i) the chronic and acute exposure of study subjects should be distinguished; (ii) the exposure history should be mapped including place of residence during the life and prenatal development; (iii) changes of epigenetic markers should be monitored over time. In summary, investigation of human adaptation to the environment, one of the most important processes of survival, is a new challenge for future research in the field of human biomonitoring that may change our view on the results of biomarker analyses and potential negative health impacts of the environment.
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http://dx.doi.org/10.1016/j.mrrev.2017.07.002DOI Listing
July 2017

Oxidative stress in newborns by different modes of delivery.

Neuro Endocrinol Lett 2016 Nov;37(6):445-451

Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic.

Objectives: The aim of our study is to investigate the impact of the type of delivery - vaginal vs. cesarean section on oxidative damage determined as the lipid peroxidation (15-F2t-isoprostane (15-F2t-IsoP) in the cord blood of newborns and venous blood from mothers in two localities with different levels of air pollution: Ceske Budejovice (CB), a locality with a clean air, and Karvina, a locality with high air pollution.

Resutls: In Karvina, the concentration of PM2.5 was higher than in CB in the summer 2013 (mean±SD: 20.41±6.28 vs. 9.45±3.62 µg/m3, p<0.001) and in the winter 2014 (mean±SD: 53.67±19.76 vs. 27.96±12.34 µg/m3, p<0.001). Similarly, the concentration of B[a]P was higher in Karvina than in CB in the summer 2013 (mean±SD: 1.16±0.91 vs. 0.16±0.26 ng/m3, p<0.001) and in the winter 2014 (5.36±3.64 vs. 1.45±1.19 ng/m3, p<0.001). Delivery procedures differed by the type of anesthesia; at the Cesarean section in CB was used general anesthesia in 73.8% vs. 20.8% in Karvina (p<0.001), epidural anesthesia in CB in 26.2% vs. 77.1% in Karvina (p<0.001), at vaginal delivery was local anesthesia used in CB in 58.9% vs. 14.1% in Karvina (p<0.001). In CB was oxidative stress higher after vaginal delivery (101.7±31.0 pg 15-F2t-isoP/ml plasma) vs. Cesarean section (83.9±26.9 pg 15-F2t-isoP/ml plasma, p<0.001), no difference between the type of delivery was observed in Karvina.

Conclusion: No difference between the types of delivery was observed in mothers in CB as well as in Karvina. Oxidative stress in newborns in Karvina was significantly affected by the concentrations of PM2.5 and B[a]P in the polluted air.
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November 2016

Impact of Air Pollution to Genome of Newborns.

Cent Eur J Public Health 2016 Dec;24 Suppl:S40-S44

University of South Bohemia, České Budějovice, Czech Republic.

The Northern Moravia Region is the most polluted region in the Czech Republic by particulate matter (PM) and carcinogenic polycyclic aromatic hydrocarbons (c-PAHs) as benzo[a]pyrene (B[a]P) by heavy industry and local heating. This specific situation was used to study the impact of air pollution on newborns in the exposed Karviná district and control district of České Budějovice. Biological material from newborns and mothers was collected in summer and winter seasons. This project is highly detailed, analyzing the concentrations of PAHs in ambient air and diet, in human breast milk, in the urine of mothers and newborns, using biomarkers of genetic damage as DNA adducts and gene expression analysis, biomarkers of oxidative stress as 8-oxodG adducts and lipid peroxidation (15-F2t-isoprostane immunoassay). All 400 children, for whom the biomarker data at delivery were obtained, will be followed for morbidity up to 2 years of age. The Northern Moravia Region seems to be to be a model area for studying the long-term impact of human health exposure to c-PAHs. Our observations will indicate possible genetic and oxidative damage in newborns, which may significantly affect their morbidity.
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http://dx.doi.org/10.21101/cejph.a4536DOI Listing
December 2016

Micronucleus frequency and content in healthy relatives of cancer patients.

Biomarkers 2017 Nov 19;22(7):667-673. Epub 2017 Jan 19.

b Department of Genetic Ecotoxicology , Institute of Experimental Medicine, Academy of Sciences of the Czech Republic , Prague , Czech Republic.

Objective: To compare chromosomal damage in lymphocytes of individuals who did or did not report first-degree relatives with cancer.

Materials And Methods: Cases and controls (68 each) were matched for sex, age and radon exposure. Chromosomal damage was quantified as frequency of micronucleus-containing cells and proportion of centromere-free micronuclei.

Results: Individuals not reporting cancer in their families showed lower values of both the frequency of micronucleus-containing cells (n.s.) and the proportion of centromere-free micronuclei (p < 0.05) in some subgroups, but not in all.

Conclusion: The chromosomal damage observed may be due to inheritable genomic instability, but environmental influences cannot be excluded.
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http://dx.doi.org/10.1080/1354750X.2016.1276627DOI Listing
November 2017

Evaluation of 11 polycyclic aromatic hydrocarbon metabolites in urine of Czech mothers and newborns.

Sci Total Environ 2016 Oct 29. Epub 2016 Oct 29.

University of Chemistry and Technology, Prague, Faculty of Food and Biochemical Technology, Department of Food Analysis and Nutrition, Technicka 3, 166 28 Prague, Czech Republic. Electronic address:

Polycyclic aromatic hydrocarbons (PAHs) represent a large group of ubiquitous contaminants of the environment, including food chain where they are released as by-products of incomplete combustion of an organic matter. Epidemiological studies have shown that exposure to PAHs correlated with increased incidence of cancer. Carcinogenicity is associated mainly with metabolites that are formed during metabolic degradation of these substances in exposed organism. In this study monohydroxylated PAHs (OH-PAHs), the major metabolites excreted into urine, were determined in 531 urine samples collected from mothers and their newborns from two localities of the Czech Republic - heavily air polluted Karvina and control locality of Ceske Budejovice and in two sampling rounds - August-October 2013 (summer, less air polluted season) and January-April 2014 (winter, more air polluted season). From all targeted analytes, naphthalene-2-ol was the most abundant compound present in 100% of the samples and it represented also the analyte with the highest concentration. Median concentration of ΣOH-PAHs in the urine of children was on average 1.6 times lower compared to the respective mother which correlates with higher intake of PAHs by mothers. ΣOH-PAHs concentrations determined in mothers' urine collected in the summer were comparable in both localities. No significant increase occurred in Ceske Budejovice in winter, while in samples from the Karvina region a statistically significant difference (α=0.05) in the amount of ΣOH-PAHs was observed. The median concentrations of ΣOH-PAHs in mothers' urine samples in the winter were 1.5 times higher than in the summer in the same locality. The amounts of ΣOH-PAHs in newborns' urine from Karvina in the winter season were 1.5 times higher than in the summer collected in the same locality and 3.3 times higher when compared with the less polluted locality of Ceske Budejovice.
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http://dx.doi.org/10.1016/j.scitotenv.2016.10.165DOI Listing
October 2016

Systematic review of the use of the lymphocyte cytokinesis-block micronucleus assay to measure DNA damage induced by exposure to polycyclic aromatic hydrocarbons.

Mutat Res 2016 Oct - Dec;770(Pt A):162-169. Epub 2016 Jul 28.

Institute of Experimental Medicine AS CR, Prague, Czech Republic.

The effect of exposure to polycyclic aromatic hydrocarbons (PAHs) to induce micronuclei (MN) measured using the lymphocytes cytokinesis-block micronucleus (CBMN) assay were evaluated in 34 studies according to the exposure: 20 studies in coke oven workers, 7 studies in different occupational exposures as alluminium industry workers, rubber factory workers, road construction workers, airport workers and diesel exposed workers, 6 studies on environmentaly exposed groups as police, volunteers and children. Reviewed papers indicate that the CBMN assay is a sensitive biomarker of PAHs exposure in polluted air. Reviewed studies confirmed previous conclusions, that the frequency of MN measured using the lymphocyte CBMN is not significantly affected by smoking, females are more sensitive to PAHs than males, the frequency of MN is increased with age.
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http://dx.doi.org/10.1016/j.mrrev.2016.07.009DOI Listing
May 2017

Mapping the factors affecting the frequency and types of micronuclei in an elderly population from Southern Bohemia.

Mutat Res 2016 Nov - Dec;793-794:32-40. Epub 2016 Oct 26.

Institute of Radiology, Toxicology and Civil Protection, University of South Bohemia, 37005 Ceske Budejovice, Czechia.

The micronucleus assay is one of the most common methods used to assess chromosomal damage (losses or breaks) in human peripheral blood lymphocytes (PBL) in genetic toxicology. Most studies have focused on analyzing total micronuclei (MN), but identifying the content of MN can provide more detailed information. The main aim of this study was to map the factors affecting the frequency and types of micronuclei in binucleated cells (BNC) in elderly population. Fluorescence in situ hybridization using Human Pan Centromeric Chromosome Paint was used to identify centromere positive (CEN+) or centromere negative (CEN-) MN. A group of 95 men from Southern Bohemia, Czech Republic (average age 68.0±6.8 years) was followed repeatedly, in spring and fall 2014. The study participants were former workers of the uranium plant "MAPE Mydlovary" (processing uranium ore from 1962 to 1991), and controls. The general profile of individual types of MN, and the effect of the season, former uranium exposure, age, smoking status, weight, and X-ray examination on the level and type of MN were analyzed. The results of this study showed: (i) a stable profile of BNC with MN based on the number of MN during two seasons; (ii) an increase of the number of CEN+ MN from spring to fall; (iii) a lower frequency of the total MN in the exposed group than in controls with a significant difference in the percentage of aberrant cells (%AB.C.) in the fall; (iv) no clear effect of age, smoking and BMI on DNA damage in this group; (v) lower DNA damage levels in former uranium workers who received X-ray examination later in life. In summary, the results indicate a trend of seasonal changes of individual types of MN and suggest that former exposure can have a protective effect on the level of DNA damage in case of future exposure.
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http://dx.doi.org/10.1016/j.mrfmmm.2016.10.004DOI Listing
May 2017

DNA Damage Potential of Engine Emissions Measured In Vitro by Micronucleus Test in Human Bronchial Epithelial Cells.

Basic Clin Pharmacol Toxicol 2017 Sep 6;121 Suppl 3:102-108. Epub 2017 Jan 6.

Department of Genetic Toxicology and Nanotoxicology, Institute of Experimental Medicine, Czech Academy of Sciences, Prague, Czech Republic.

Internal combustion engine emissions belong among the major anthropogenic sources of air pollution in urban areas. According to the International Agency for Research on Cancer, there is sufficient evidence of the carcinogenicity of diesel exhaust in human beings. Although alternative fuels, mainly biodiesel, have recently become popular, little is still known about the genotoxicity of emissions from these fuels. We analysed DNA damage expressed as the frequency of micronuclei (MN) in human bronchial epithelial cells (BEAS-2B), induced by extractable organic matter (EOM; tested concentrations: 1, 10 and 25 μg/ml) obtained from particle emissions from various blends of biodiesel with diesel fuels (including neat diesel fuel (B0), a blend of 70% B0 and 30% biodiesel (B30) and neat biodiesel (B100)). We also tested the effect of selected diesel exhaust organic/genotoxic components [benzo[a]pyrene (B[a]P) concentrations: 25, 100 and 200 μM; 1-nitropyrene (1-NP) concentrations: 1, 5 and 10 μM; 3-nitrobenzanthrone (3-NBA) concentrations: 1, 5 and 50 μM]. The cells were treated with the compounds for 28 and 48 hr. Our results showed that most of the tested compounds (except for the 25 μM B[a]P, 28-hr treatment) significantly increased MN frequency. The genotoxicity of EOMs from the engine emissions of diesel and biodiesel engines was comparable. Both nitro-PAH compounds demonstrated higher genotoxic potential in comparison with B[a]P. Considering our results and due to increasing popularity of alternative fuels, it is prudent that the potential genotoxic effects of various fuels are investigated across engine technologies and operating conditions in a relevant model system.
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http://dx.doi.org/10.1111/bcpt.12693DOI Listing
September 2017

Perinatal health in the Danube region - new birth cohort justified.

Rev Environ Health 2017 Mar;32(1-2):9-14

In 2013-2015, a consortium of European scientists - NEWDANUBE - was established to prepare a birth cohort in the Danube region, including most of the countries with the highest air pollution in Europe, the area being one-fifth of the European Union's (EU's) territory, including 14 countries (nine EU member states), over 100 million inhabitants, with numerous challenges: big socioeconomic disparities, and a region-specific environmental pollution. The consortium reflects the EU Strategy for the Danube Region Strategy (2010), which identified 11 thematic Priority Areas - one of which is the environmental risks. Birth cohorts have been established in all other areas of Europe and collaborative efforts in promoting maternal and fetal health by minimizing the environmental exposures have been initiated with national, European, and international financial support. A birth cohort in the Danube area could apply the established methodologies for prenatal exposure and birth outcome measurements and establish a platform for targeted health promotion in couples planning pregnancies. The consortium included a strong socioeconomic part focusing on the participant's active registration of exposures to environmental toxicants and health indicators of disease and wellbeing, combined with investigation of their risk-reducing behavior and interventions to change their lifestyle to avoid the adverse health risks. Willingness to pay for reducing the health risks in children is also proposed to be estimated. Further collaboration and networking is encouraged as the Danube region has several decades of experience and expertise in biomonitoring adult populations exposed environmentally or occupationally. Additionally, some countries in the Danube region launched small-scale birth cohorts encouraged by participation in several ongoing research projects.
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http://dx.doi.org/10.1515/reveh-2016-0038DOI Listing
March 2017

Impact of air pollution on oxidative DNA damage and lipid peroxidation in mothers and their newborns.

Int J Hyg Environ Health 2016 08 31;219(6):545-56. Epub 2016 May 31.

Department of Genetic Ecotoxicology, Institute of Experimental Medicine, AS CR, Prague, Czech Republic. Electronic address:

Ambient air particulate matter (PM) represents a class of heterogeneous substances that form one component of air pollution. Oxidative stress has been implicated as an important action mechanism for PM on the human organism. Oxidative damage induced by reactive oxygen species (ROS) may affect any cellular macromolecule. The aim of our study was to investigate the impact of air pollution on oxidative DNA damage [8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG)] and lipid peroxidation [15-F2t-isoprostane (15-F2t-IsoP)] in the urine and blood from mothers and newborns from two localities with different levels of air pollution: Ceske Budejovice (CB), a locality with a clean air, and Karvina, a locality with high air pollution. The samples from normal deliveries (38-41 week+) of nonsmoking mothers and their newborns were collected in the summer and winter seasons. Higher PM2.5 concentrations were found in Karvina than in CB in the summer 2013 (mean±SD: 20.41±6.28 vs. 9.45±3.62μg/m(3), P<0.001), and in the winter 2014 (mean±SD: 53.67±19.76 vs. 27.96±12.34μg/m(3), P<0.001). We observed significant differences in 15-F2t-IsoP levels between the summer and winter seasons in Karvina for newborns (mean±SD: 64.24±26.75 vs. 104.26±38.18pg/ml plasma, respectively) (P<0.001). Levels of 8-oxodG differed only in the winter season between localities, they were significantly higher (P<0.001) in newborns from Karvina in comparison with CB (mean±SD: 5.70±2.94 vs. 4.23±1.51 nmol/mmol creatinine, respectively). The results of multivariate regression analysis in newborns from Karvina showed PM2.5 concentrations to be a significant predictor for 8-oxodG excretion, PM2.5 and B[a]P (benzo[a]pyrene) concentrations to be a significant predictor for 15-F2t-IsoP levels. The results of multivariate regression analysis in mothers showed PM2.5 concentrations to be a significant predictor of 8-oxodG levels.
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http://dx.doi.org/10.1016/j.ijheh.2016.05.010DOI Listing
August 2016

Relationship between atmospheric pollution in the residential area and concentrations of polycyclic aromatic hydrocarbons (PAHs) in human breast milk.

Sci Total Environ 2016 08 22;562:640-647. Epub 2016 Apr 22.

University of Chemistry and Technology, Prague, Faculty of Food and Biochemical Technology, Department of Food Analysis and Nutrition, Technicka 3, 166 28 Prague 6, Czech Republic.

Human milk is an important source of beneficial nutrients and antibodies for newborns and infants and, under certain circumstances, its analysis may provide information on mothers' and infants' exposure to various contaminants. In the presented study, we have introduced the new analytical approach for analysis of 24 highly occurring polycyclic aromatic hydrocarbons (PAHs) in this indicator matrix. The sample preparation procedure is based on an ethyl acetate extraction of milk; the transfer of analytes into an organic layer is enhanced by addition of inorganic salts, i.e. sodium chloride and magnesium sulphate. Following the clean-up of a crude extract on silica SPE columns, gas chromatography coupled to triple quadrupole mass spectrometry is used for PAH identification and quantitation. The average recoveries of targeted PAHs from spiked samples were in the range of 68-110% with repeatabilities below 30% and method quantitation limits ranging from 0.03 to 0.3ng/g lipid weight. This newly validated method was successfully applied for analyses of 324 human milk samples collected from nonsmoking women during two sampling periods (summer and winter) in two residential areas in the Czech Republic differing in atmospheric pollution by PAHs. From 24 targeted analytes 17 were detected at least in one sample. Phenantherene, fluoranthrene, pyrene and fluorene were the most abundant compounds found at average concentration of 13.81, 1.80, 0.86, and 2.01ng/g lipid weight respectively. Comparing the data from two sampling periods, in both areas higher concentrations were measured in samples collected during winter. Also in the highly industrialized locality with heavily contaminated air PAH amounts in milk were higher than in the control locality. These first data on PAH concentrations in human milk collected in the Czech Republic are comparable with measurements for nonsmoking women reported earlier in the United States but significantly lower than results from China, Turkey or Italy.
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http://dx.doi.org/10.1016/j.scitotenv.2016.04.013DOI Listing
August 2016