Institute of Experimental Medicine CAS

Department of Genetic Toxicology and Nanotoxicology

Head:

Jan Topinka, PhD., DSc.

E-mail: jtopinka@biomed.cas.cz
Phone: +420 241 062 675,
+420 241 062 763
Fax: +420 241 062 785

Department of Genetic Toxicology and Nanotoxicology (DGTN) is focused on the mechanisms of toxic effects of engineered nanoparticles as well as combustion generated fine and ultrafine particles. Major attention is paid to the interaction of particles and their components with biomolecules inhuman cell lines. The methods include various tests of cytotoxicity, the detection of reactive oxygen species and oxidative damage of DNA, proteins and lipids (ELISA), analyzes of genotoxicity (Comet assay, DNA adducts) and clastogenic effects (micronucleus test and cytogenetic analysis by FISH),as well as analyzes of protein expression (western blotting) and DNA repair activity (NER and NHEJ). To get more insight into the mechanism of biological effects of particles or their extracts, the toxicogenomic methods (microarrays and next generation sequencing) and RT-PCR are used. Most ofthese tests are also available to external users from research, universities and academia via the Research Infrastructure NanoEnviCz (www.nanoenvicz.cz). DGTN also concentrates on the mechanisms of adverse effects of engine emissions particularly under real traffic condition (www.medetox.cz). Another topic includes molecular epidemiology studies analyzing the effect of environmental pollution on human health.

Deputy Head:

Pavel Rössner Jr., PhD.
E-mail: prossner@biomed.cas.cz
Phone: +420 241 062 763

Research Scientists:

Helena Líbalová, PhD.
Božena Novotná, PhD.
Martin Pechout, PhD.
Pavel Rössner Jr., PhD.
Andrea Rössnerová, PhD.
Radim J. Šrám, MD, DrSc.
Vlasta Švecová, PhD.
Jan Topinka, PhD., DSc.
Veronika Vlková, PhD.
Michal Vojtíšek, Assoc. Prof., PhD.

PhD. Students:

Antonín Ambrož, MSc
Táňa Brzicová, MSc
Tereza Červená, MSc
Kateřina Hoňková, MSc
Jitka Pavlíková, MSc
Jitka Sikorová, MSc

Research Assistants:

Fatima Elzeinová, MSc
Hasmik Margaryan, MSc
Alena Milcová, MSc
Zuzana Nováková, MSc
Michaela Pokorná, MSc
Věra Topinková, MSc
Kristýna Vrbová, MSc

Technican:

Jolana Vaňková

Important results in 2017

1. Ultrafine and Fine Particles and Hospital Admissions in Central Europe. Results from the UFIREG Study

We investigated effects of ultrafine and fine particulate matter on cause-specific hospital admissions in Central and Eastern European cities. We found that a 2,750 particles/cm3 increase of ultrafine particles caused an increase in the risk of respiratory hospital admissions. We also found increases in the risk of cardiovascular and respiratory admissions associated with exposure to particulate matter of aerodynamic diameter < 2.5 µm.

ogtn-vyzn-vysl-1-2017a

Praticles size and their deposition in the respiratory tract ( http://www.ufireg-central.eu).

Publikace:
Lanzinger S, Schneider A, Breitner S, Stafoggia M, Erzen I, Dostal M, Pastorkova A, Bastian S, Cyrys J, Zscheppang A, Kolodnitska T, Peters A; UFIREG study group: (2016) Ultrafine and Fine Particles and Hospital Admissions in Central Europe. Results from the UFIREG Study. Am J Respir Crit Care Med.194(10):1233-1241. IF 13.204

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

The main aim of this review was to provide a comprehensive overview of the last decade of Czech biomonitoring research, concerning the effect of various levels of air pollution and radiation, on the differently exposed population groups. A detailed analysis of data 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.

ogtn-vyzn-vysl-1-2017b

A model of epigenetic mechanism providing the link between changes of environmental factors during life and the levels of DNA damage.

Publikace:
Rössnerová, A., Pokorná, M., Švecová, V., Šrám, R., Topinka, J., Zölzer, F., Rössner, P.: (2017) Adaptation of the human population to the environment: Current knowledge, clues from Czech cytogenetic and "omics" biomonitoring studies and possible mechanisms. Mutation Research-Reviews in Mutation Research. 773: 188-203. IF=5.5. doi: 10.1016/j.mrrev.2017.07.002. Epub 2017 Jul 12. Review.

3. Blends of butanol and hydrotreated vegetable oils as drop-in replacement for diesel engines: Effects on combustion and emissions

We investigated the performance of a mix of two emerging biofuels, butanol and hydrotreated vegetable oil (HVO), in an Iveco Tector diesel engine. HVO, a possible drop-in fuel for diesel engines features excellent combustion and emissions characteristics. All biofuels exhibited, relative to diesel fuel, a decrease in the concentration of particulate PAHs and n-alkanes in emissions, while the concentrations of hopanes and steranes originated from lubricating oil were comparable across all fuels. Cold starts yielded about 15% higher concentrations of both particulate matter and particulate organic compounds in emissions than hot startsparticulate matter and particulate organic compounds in emissions than hot starts.

ogtn-vyzn-vysl-3-2017

Sampling instrumentation Digitel for particulate engine emissions  

Publikace:
Vojtíšek-Lom, M., Beránek, V., Mikuška, P., Křůmal, K., Coufalík, P., Sikorová, J., Topinka, J.: (2017) Blends of butanol and hydrotreated vegetable oils as drop-in replacement for diesel engines: Effects on combustion and emissions. Fuel, 197: 407-421.  IF 4,601

 

Important results in 2016

1. Comparative Analysis of Toxic Responses of Organic Extracts from Diesel and Selected Alternative Fuels Engine Emissions in Human Lung BEAS-2B Cells

Exhaust particles from four different diesel/biodiesel fuels were collected, organic compounds were extracted and human lung cells were exposed  to each extract. Chemical analysis revealed that extract from neat hydrotreated vegetable oil NexBTL contained the lowest content of carcinogenic PAHs and gene expression profiling identified deregulation of numerous genes and processes common for all extract as well as specific for each extract. Despite subtle differences in overall toxic effects induced by different diesel or alternative fuels, NexBTL extract exhibited the weakest toxicity comparing to others.

ogtn-vyzn-vysl-1-2016

Sampling, organic extraction and toxicogenomic analysis of different diesel/alternative fuel exhaust particles.
Exhaust particles from standard diesel (B0), biodiesel (methylesters of rapeseed oil) in its neat form (B100) and 30% by volume blend with diesel fuel (B30), and neat hydrotreated vegetable oil (NEXBTL100) was collected and characterized. Global gene expression changes were analyzed in BEAS-2B cells following 4 h and 24 h treatment with orgaic compounds extracted from particles. The subtoxic concentrations of 50 µg extract/mL induced a similar molecular response. The common processes induced after 4 h treatment included antioxidant defense, metabolism of xenobiotics and lipids, suppression of pro-apoptotic stimuli, or induction of plasminogen activating cascade; 24 h treatment affected fewer processes, particularly those involved in detoxification of xenobiotics, including PAHs. The majority of distinctively deregulated genes detected after both 4 h and 24 h treatment were induced by NEXBTL100; the deregulated genes included, e.g., those involved in antioxidant defense and cell cycle regulation and proliferation.

Publication:
Helena Libalova, Pavel Rossner Jr., Kristyna Vrbova, Tana Brzicova, Jitka Sikorova, Michal Vojtisek-Lom, Vit Beranek, Jiri Klema, Miroslav Ciganek, Jiri Neca, Katerina Pencikova, Miroslav Machala, Jan Topinka:(2016) Comparative Analysis of Toxic Responses of Organic Extracts from Diesel and Selected Alternative Fuels Engine Emissions in Human Lung BEAS-2B Cells. International Journal of Molecular Sciences. IF 3.257

2. Urinary 8-oxo-7,8-dihydro-2‘-deoxyguanosine analysis by an improved ELISA: An inter-laboratory comparison study

We performed an inter-laboratory comparison of 8-oxo-7,8-dihydro-2‘-deoxyguanosine by ELISA using standardized conditions, compared the ELISA results with high-performance liquid chromatography-tandem mass spectrometry and performed identification of compounds that may contribute to the discrepancy between methods. Assay standardization significantly improved inter-laboratory agreement, although some variability caused by aromatic and heterocyclic compounds and saccharides is still observed.

ogtn-vyzn-vysl-2-2016

An improved ELISA to assess urinary 8-oxo-7,8-dihydro-2‘-deoxyguanosine (8-oxodG)
Using standardized conditions urinary 8-oxodG levels were analyzed. Assay standardization significantly decreased inter-laboratory variability of the assay.

Publication:
Rössner, P., Orhan, H., Koppen, G., Sakai, K., Santella, R.M., Ambrož, A., Rossnerová, A., Šrám, R.,Ciganek, M., Neca, J., Arzuk, E., Mutlu, N., Cooke, M.S.: (2016) Urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine analysis by an improved ELISA: An inter-laboratory comparison study. Free Radic. Biol. Med.,  22;95: 169-179. IF 5.784

3. The impact of silica encapsulated cobalt zinc ferrite nanoparticles on DNA, lipids and proteins of rat bone marrow mesenchymal stem cells

Cobalt-zinc-ferrite nanoparticles (NPs) encapsulated by amorphous silica were tested to assess their effect on DNA, lipids and proteins in rat mesenchymal stem cells. No significant cytotoxic effects were observed, except for the highest dose of CZF-NPs, that slowed down cell proliferation and induced damage to DNA, lipids and proteins. The results suggest that the silica-coated CZF-NPs, when applied at a non-toxic dose, represent a promising contrast agent for cell labeling for magnetic resonance analysis.

Publication:
Novotná, B., Turnovcová, K., Veverka, P., Rössner, P. Jr., Bagryantsevá, Y., Herynek, V., Zvatora, P., Vosmanská, M., Klementová, M., Syková, E., Jendelová, P.: (2016)The impact of silica encapsulated cobalt zinc ferrite nanoparticles on DNA, lipids and proteins of rat bone marrow mesenchymal stem cells. Nanotoxicology, 10(6): 662-670. IF 7.913

 

Important results in 2015

1. Analysis of genetic damage in lymphocytes of former uranium processing workers

The frequency of cells containing micronuclei (MN) and the presence of centromeres in the MN were analyzed in lymphocytes of men from Southern Bohemia (former workers of a former uranium processing plant „MAPE Mydlovary“ and controls). No differences were found between formerly exposed workers and the control group. Moreover former workers with X-ray examination had significantly lower level of DNA damage than the control group. Possible reason of this results may be adaptation of the organism.

2015topinka1

Examples of cytochalasin-B-blocked human peripheral blood lymphocytes stained with DAPI (blue) and Pan Centromeric probes with FITC (green): (a) Overall view (100x), (b) binucleated cell (BNC) with one centromere-positive (CEN+) micronucleus (MN) (1000x), (c) BNC with one centromere-negative (CEN-) MN (1000x) and (d) BNC with two MN, both CEN- (1000x).

Publication:
Zölzer, F., Havránková, R., Freitinger Skalická, Z., Rössnerová, A., Šrám, R.J.: (2015) Analysis of Genetic Damage in Lymphocytes of Former Uranium Processing Workers. Cytogenet Genome Res. 2015; 147 (1): 17-23

2. Day-to-day variability of toxic events induced by organic compounds bound to size segregated atmospheric aerosol

The temporal variability of size-segregated aerosol mass collected on a daily basis during the winter period in highly polluted districts of Ostrava city as well as toxic effects of organic compounds extracted from each size fraction were quantified. We revealed that upper accumulation mode fraction (0.5 < dae < 1 μm) comprises most of the aerosol mass and contained 44% of total c-PAHs while ultrafine fraction (< 0.17 μm) contained only 11% of c-PAHs. DNA adduct levels and dioxin-like activity strongly correlated with both aerosol mass and c-PAH concentrations suggesting genotoxicity as a major toxic effect of organic compounds bound to size-segregated aerosol.

2015topinka2

(a) Sum of c-PAH concentrations in four aerosol fractions per mg of the size fraction mass. c-PAHs include benz[a]anthracene, chrysene, benzo[k]fluoranthene, benzo[a]pyrene, dibenz[a,h]anthracene and indeno[1,2.3-cd]pyrene.
(b) Total DNA adduct levels induced by organic extracts from size-segregated aerosols in an acellular system (calf thymus DNA) per mg of the size fraction mass. A strong positive correlation was found between c-PAH content in different aerosol size fractions and DNA adducts (R: 0.62 – 0.86).

Publication:
Topinka, J., Rossner, P. Jr., Milcová, A., Schmuczerová, J., Pěnčíková, K., Rossnerová, A., Ambrož, A., Štolcpartová, J., Bendl, J., Hovorka, J., Machala, M.: (2015) Day-to-day variability of toxic events induced by organic compounds bound to size segregated atmospheric aerosol. Environ. Pollut. 202: 135-145.

3. Reduced gene expression levels after chronic exposure to high concenrations of air pollutants

We analyzed the effect of air pollution on gene expression in subjects living in Prague and in the polluted Ostrava region. We expected to observe changes in expression of DNA repair genes in subjects from the Ostrava region. Unexpectedly, the changes were found in Prague subjects, particularly in genes associated with immune response and neurodegenerative diseases. The results suggest that chronic exposure to air pollution may result in adaptation of the organism with possible negative health effects.

2015topinka3-en

Pathways associated with air pollution in subjects from Prague and the Ostrava region. The figure shows both the pathways associated with location only and the pathways associated with exposure to air pollution (B[a]P – benzo[a]pyrene, PM2.5 – particulate matter of aerodynamic diameter < 2.5 µm).

Publication:
Rossner, Jr. P., Tulupová, E., Rossnerová, A., Líbalová, H., Hoňková, K., Gmuender, H., Pastorková, A., Švecová, V., Topinka, J., Šrám, R.J.: (2015) Reduced gene expression levels after chronic exposure to high concentrations of air pollutants. Mutat Res. 780:60-70.

2018

Leoni, C., Pokorná, P., Hovorka, J., Masiol, M., Topinka, J., Zhao, Y., Křůmal, K., Cliff, S., Mikuška, P., Hopke, P.K.: (2018) Source apportionment of aerosol particles at a European air pollution hot spot using particle number size distributions and chemical composition. Environmental Pollution. 234: 145-154. IF=5.099

Mukherjee, S.P., Bondarenko, O., Kohonen, P., Andón, F.T., Brzicová, T., Gessner, I., Mathur, S., Bottini, M., Calligari, P., Stella, L., Kisin, E., Shvedova, A., Autio, R., Salminen-Mankonen, H., Lahesmaa, R., Fadeel, B.: (2018) Macrophage sensing of single-walled carbon nanotubes via Toll-like receptors. Scientific Reports. 8: 1115. IF=4.259

Libalova, H ., Costa, P.M., Olsson M., Farcal, L., Ortelli, S., Blosi, M., Topinka, J., Costa, A.L., Fadeel, B.: (2018) Toxicity of surface-modified copper oxide nanoparticles in a mouse macrophage cell line: Interplay of particles, surface coating and particle dissolution. Chemosphere. 196: 482-493. IF=4.208

Fernandéz, D., Sram, R.J., Dostal, M., Pastorkova, A., Gmuender, H., Choi, H.: (2018) Modeling unobserved Heterogeneity in susceptibility to ambient benzo[a]pyrene concentration among children with allergic asthma using an unsupervised learning algorithm. Int. J. Environ. Res. Public Health. 15, 106. IF=2.101

Libalova, H., Milcova, A., Cervena, T., Vrbova, K., Rossnerova, A., Novakova, Z., Topinka, J., Rossner, P., Jr. : (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 Gen Tox En. 827:50-58. IF=2.133

2017

Collins, A.R., Annangi, B., Rubio, L., Marcos, R., Dorn, M., Merker, C., Estrela-Lopis, I., Cimpan, M.R., Ibrahim, M., Cimpan, E., Ostermann, M., Sauter, A., Yamani, N.E., Shaposhnikov, S., Chevillard, S., Paget, V., Grall, R., Delic, J., de-Cerio, F.G., Suarez-Merino, B., Fessard, V., Hogeveen, K.N., Fjellsbø, L.M., Pran, E.R., Brzicová, T., Topinka, J., Silva, M.J., Leite, P.E., Ribeiro, A.R., Granjeiro, J.M., Grafström, R., Prina-Mello, A., Dusinska, M.: (2017) High throughput toxicity screening and intracellular detection of nanomaterials. Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology. 9(1):UNSP e1413.

Červená, T., Rössnerová, A., Sikorová, J. , Beránek, V., Vojtíšek-Lom, M., Ciganek, M., Topinka, J., Rössner, P. Jr.: (2017) DNA Damage Potential of Engine Emissions Measured In Vitro by Micronucleus Test in Human Bronchial Epithelial Cells. Basic & Clinical Pharmacology & Toxicology. 121 (SI): 102-108.

Fishbain, B., Lerner, U., Castell, N., Cole-Hunter, T., Popoola, O., Broday, D.M., Iñiguez, T.M., Nieuwenhuijsen, M., Jovasevic-Stojanovic, M., Topalovic, D., Jones, R.L., Galea. K.S., Etzion, Y., Kizel, F., Golumbic, Y.N., Baram-Tsabari, A., Yacobi, T., Drahler, D., Robinson, J.A., Kocman, D., Horvát, M., Švecová, V., Arpaci, A., Bartonová, A.: (2016) An evaluation tool kit of air quality micro-sensing units. Science of the Total Environment. 575: 639-648.

Choi, H., Tabashidze, N., Rössner, P., Dostál, M., Pastorková, A., Kong, S.W., Gmuender, H., Šrám, R.: (2017) Altered vulnerability to asthma at various levels of ambient Benzo[a]Pyrene by CTLA4, STAT4 and CYP2E1 polymorphisms. Environmental Pollution. 231: 1134-1144.

Lanzinger, S., Schneider A., Breitner, S., Stafoggia, M., Erzen, I., Dostál, M., Pastorková, A., Bastian, S., Cyrys, J., Zscheppang. A., Kolodnitska, T., Peters, A.: (2016) Ultrafine and Fine Particles and Hospital Admissions in Central Europe. Results from the UFIREG Study. American Journal of Respiratory and Critical Care Medicine. 194(10): 1233-1241.

Novotná, B. , Herynek, V., Rössner ml., P., Turnovcová, K., Jendelová, P.: (2017) The effects of grafted mesenchymal stem cells labeled with iron oxide or cobalt-zinc-iron nanoparticles on the biological macromolecules of rat brain tissue extracts. International Journal of Nanomedicine. 12: 4519-4526.

Rössnerová, A., Pokorná, M., Švecová, V., Šrám, R., Topinka, J. , Zölzer, F., Rössner, P.: (2017) Adaptation of the human population to the environment: Current knowledge, clues from Czech cytogenetic and "omics" biomonitoring studies and possible mechanisms. Mutation Research-Reviews in Mutation Research. 773: 188-203.

Šrám, R.J., Rössner, P., Rössnerová, A., Dostál, M., Milcová, A., Švecová, V. , Pulkrabová, J., Hajšlová, J., Velemínský, M.: (2016) Impact of Air Pollution to Genome of Newborns. Am. J. Respir. Crit. Care Med., 24 : S40-S44.

Urbancová, K., Lanková, D., Rössner ml., P., Rössnerová, A., Švecová, V., Tomaniová, M., Veleminský Jr., M., Šrám, R., Hajslová, J., Pulkrabová, J.: (2017) Evaluation of 11 polycyclic aromatic hydrocarbon metabolites in urine of Czech mothers and newborns. Science of the Total Environment. 577: 212-219.

Veleminský , M., Hanzl, M., Šrám, R.: (2017) The impact of air pollution in the Southern Bohemia Region on fetuses and newborns. Neuroendocrinology Letters. 37(2 ): 52-57.

Veleminský, M., Ambrož, A., Rössner, P., Rössnerová, A., Švecová, V., Milcová, A., Dostál, M., Pastorková, A., Pulkrabová, J., Hajslová, J., Solanský, I., Hanzl, M., Šrám, R.: (2016) Oxidative stress in newborns by different modes of delivery. Neuroendocrinology Letters. 37(6): 445-451.

Vojtíšek-Lom, M., Beránek, V., Mikuška, P., Křůmal, K., Coufalík, P., Sikorová, J., Topinka, J.: (2017) Blends of butanol and hydrotreated vegetable oils as drop-in replacement for diesel engines: Effects on combustion and emissions. Fuel. 197: 407-421.

Zapletal, O, Tylichová, Z., Neča, J., Kohoutek, J., Machala, M., Milcová, A., Pokorná, M., Topinka, J., Moyer, M.P., Hofmanová, J., Kozubík, A., Vondráček, J.: (2017) Butyrate alters expression of cytochrome P450 1A1 and metabolism of benzo[a]pyrene via its histone deacetylase activity in colon epithelial cell models. Archives of Toxicology. 91(5): 2135-2150.

Zölzer, F., Křížová, M., Skalická, Z.F., Rössnerová, A., Šrám, R.: (2017) Micronucleus frequency and content in healthy relatives of cancer patients. Biomarkers. 22(7): 667-673.

2016

Ambrož, A., Vlková, V., Rössner, P. Jr., Rössnerová, A., Švecová, V., Milcová, A. , Pulkrabová, J., Hajslová, J., Veleminský, M. Jr., Solanský, I., Šrám, R.: (2016) Impact of air pollution on oxidative DNA damage and lipid peroxidation in mothers and their newborns. Int. J. Hyg. Environ. Health., 219 (6): 545-556.

Andersen, Z. J., Šrám, R. J., Ščasný, M., Gurzau, E. S., Fucic, A., Gribaldo, L., Rossner,P. Jr., Rossnerová, A., Braun Kohlová, M., Máca, V., Zvěřinová,I.,Gajdosová, D., Moshammer, H., Rudnai, P., Knudsen, L. E.: (2016) Newborns health in the Danube Region: Environment, biomonitoring, interventions and economic benefits in a large prospective birth cohort study. Environ. Int., 88: 112-122.

Collins, A.R., Annangi, B., Rubio, L., Marcos, R., Dorn, M., Merker, C., Estrela-Lopis, I., Cimpan, M.R., Ibrahim, M., Cimpan, E., Ostermann, M., Sauter, A., Yamani, N.E., Shaposhnikov, S., Chevillard, S., Paget, V., Grall, R., Delic, J., de-Cerio, F.G., Suarez-Merino, B., Fessard, V., Hogeveen, K.N., Fjellsbø, L.M., Pran, E.R., Brzicová, T., Topinka, J., Silva, M.J., Leite, P.E., Ribeiro, A.R., Granjeiro, J.M., Grafström, R., Prina-Mello, A., Dusinska, M.: (2016) High throughput toxicity screening and intracellular detection of nanomaterials. Wiley Interdiscip. Rev.-Nanomed. Nanobiotechnol., IN PRESS

Červená, T., Rössnerová, A., Sikorová, J. , Beránek, V., Vojtíšek-Lom, M., Ciganek, M., Topinka, J., Rössner, P. Jr.: (2016) DNA Damage Potential of Engine Emissions Measured In Vitro by Micronucleus Test in Human Bronchial Epithelial Cells. Basic Clin. Pharmacol. Toxicol., IN PRESS

Fishbain, B., Lerner, U., Castell, N., Cole-Hunter, T., Popoola, O., Broday, D.M., Iñiguez, T.M., Nieuwenhuijsen, M., Jovasevic-Stojanovic, M., Topalovic, D., Jones, R.L., Galea. K.S., Etzion, Y., Kizel, F., Golumbic, Y.N., Baram-Tsabari, A., Yacobi, T., Drahler, D., Robinson, J.A., Kocman, D., Horvát, M., Švecová, V., Arpaci, A., Bartonová, A.: (2016) An evaluation tool kit of air quality micro-sensing units. Sci. Total Environ., IN PRESS

Fucic, A., Bonassi, S., Gundy, S., Lazutka, J., Šrám, R., Ceppi, M., Lucas, J.N.: (2016) Frequency of Acentric Fragments Are Associated with Cancer Risk in Subjects Exposed to Ionizing Radiation. Anticancer Res., 36(5): 2451-2457.

Ghosh, R., Rossner, P., Hoňková, K., Dostál, M., Šrám, R., Hertz-Picciotto, I.: (2016) Air pollution and childhood bronchitis: Interaction with xenobiotic, immune regulatory and DNA repair genes. Environ. Int., 87: 94-100.

Lanková, D., Urbancová, K., Šrám, R., Hajslová, J., Pulkrabová, J.: (2016) A novel strategy for the determination of polycyclic aromatic hydrocarbon monohydroxylated metabolites in urine using ultra-high-performance liquid chromatography with tandem mass spectrometry. Anal. Bioanal. Chem., 408(10): 2515-2525.

Lanzinger, S., Schneider, A., Breitner, S., Stafoggia, M., Erzen, I., Dostál, M., Pastorková, A., Bastian, S., Cyrys, J., Zscheppang, A., Kolodnitská, T., Peters, A.: (2016) Associations between ultrafine and fine particles and mortality in five central European cities - Results from the UFIREG study. Environ. Int., 88: 44-52.

Líbalová, H., Rössner, P., Vrbová, K., Brzicová, T., Sikorová, J. , Vojtíšek-Lom, M., Beranek, V., Klema, J., Ciganek, M., Neca, J., Penciková, K., Machala, M., Topinka, J.: (2016) Comparative Analysis of Toxic Responses of Organic Extracts from Diesel and Selected Alternative Fuels Engine Emissions in Human Lung BEAS-2B Cells. Int. J. Mol. Sci., 17(11): E1833.

Mordukhovich, I., Beyea, J., Herring, A.H., Hatch, M., Stellman, S.D., Teitelbaum, S.L., Richardson, D.B., Millikan, R.C. Engel, L.S., Shantakumar, S., Steck, S.E., Neugut, A.I., Rössner, P., Santella, R.M., Gammon, M.D.: (2016) Polymorphisms in DNA repair genes, traffic-related polycyclic aromatic hydrocarbon exposure and breast cancer incidence. International journal of cancer, 139 (2): 310-321.

Mordukhovich, I., Beyea, J., Herring, A.H., Hatch, M., Stellman, S.D., Teitelbaum, S.L., Richardson, D.B., Millikan, R.C., Engel, L.S., Shantakumar, S., Steck, S.E., Neugut, A.I., Rössner, P., Santella, R.M., Gammon, M.D.: (2015) Vehicular Traffic-Related Polycyclic Aromatic Hydrocarbon Exposure and Breast Cancer Incidence: The Long Island Breast Cancer Study Project (LIBCSP). Environ Health Perspect., 124(1): 30-38.

Novotná, B., Turnovcová, K. , Veverka, P., Rössner, P. Jr., Bagryantsevá, Y., Herynek, V., Zvatora, P., Vosmanská, M., Klementová, M., Syková, E., Jendelová, P.: (2016) The impact of silica encapsulated cobalt zinc ferrite nanoparticles on DNA, lipids and proteins of rat bone marrow mesenchymal stem cells. Nanotoxicology, 10(6): 662-670.

Pulkrabová, J., Stupak, M., Švarcová, A., Rössner, P., Rössnerová, A., Ambrož, A., Šrám, R., Hajslová, J.: (2016) Relationship between atmospheric pollution in the residential area and concentrations of polycyclic aromatic hydrocarbons (PAHs) in human breast milk. Sci. Total Environ., 562: 640-647.

Rössner, P., Orhan, H., Koppen, G., Sakai, K., Santella, R.M., Ambrož, A., Rossnerová, A., Šrám, R., Ciganek, M., Neca, J., Arzuk, E., Mutlu, N., Cooke, M.S.: (2016) Urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine analysis by an improved ELISA: An inter-laboratory comparison study. Free Radic. Biol. Med., 22;95: 169-179.

Rössner, P. , Strapáčová, S., Štolcpartová, J., Schmuczerová, J., Milcová, A., Neca, J., Vlková, V., Brzicová, T., Machala, M., Topinka, J.: (2016) Toxic Effects of the Major Components of Diesel Exhaust in Human Alveolar Basal Epithelial Cells (A549). Int. J. Mol. Sci., 17(9): E1393.

Rössnerová, A., Hoňková,K., Pavlíková, J. , Freitinger-Skalická, Z., Havránková,R., Solanský, I., Rössner, P. Jr., Šrám, R.J., Zölzer, F.: (2016) Mapping the factors affecting the frequency and types of micronuclei in an elderly population from Southern Bohemia. Mutat. Res.-Fundam. Mol. Mech. Mutagen., 793 - 794: 32-40.

Šrám, R.J., Švecová, V., Rössnerová, A.: (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.-Fundam. Mol. Mech. Mutagen., 770(Pt A):162-169.
Urbancová, K., Lanková, D., Rössner, P., Rössnerová, A., Švecová, V., Tomaniová, M., Veleminský, M. Jr., Šrám, R.J., Hajslová, J., Pulkrabová, J.: (2016) Evaluation of 11 polycyclic aromatic hydrocarbonmetabolites in urine of Czech mothers and newborns. Sci. Total Environ., 212-219.

Zapletal, O., Tylichová, Z., Neča, J., Kohoutek ,J., Machala, M., Milcová, A., Pokorná, M., Topinka, J., Moyer, M.P., Hofmanová, J., Kozubík, A., Vondráček, J.: (2016) Butyrate alters expression of cytochrome P450 1A1 and metabolism of benzo[a]pyrene via its histone deacetylase activity in colon epithelial cell models. Arch. Toxicol., IN PRESS

Zölzer, F., Havránková, R., Freitinger Skalická, Z., Rössnerová, A., Šrám, R.J.: (2015) Analysis of Genetic Damage in Lymphocytes of Former Uranium Processing Workers. Cytogenet. Genome Res., IN PRESS

2015

Andersen, Z. J., Šrám, R. J., Ščasný, M., Gurzau, E. S., Fucic, A., Gribaldo, L., Rossner, P. Jr., Rossnerová, A., Braun Kohlová, M., Máca, V., Zvěřinová,I.,Gajdosová, D., Moshammer, H., Rudnai, P., Knudsen, L. E.: (2016) Newborns health in the Danube Region: Environment, biomonitoring, interventions and economic benefits in a large prospective birth cohort study. Environ. Int., 88: 112-122.

Fucic, A., Bonassi, S., Gundy, S., Lazutka, J., Šrám, R., Ceppi, M., Lucas, J.N.: (2016) Frequency of Acentric Fragments Are Associated with Cancer Risk in Subjects Exposed to Ionizing Radiation. Anticancer Res., 36(5): 2451-2457.

Lanková, D., Urbancová, K., Šrám, R., Hajslová, J., Pulkrabová, J.: (2016) A novel strategy for the determination of polycyclic aromatic hydrocarbon monohydroxylated metabolites in urine using ultra-high-performance liquid chromatography with tandem mass spectrometry. Anal. Bioanal. Chem., 408(10): 2515-2525.

Pulkrabová, J., Stupak, M., Švarcová, A., Rössner, P., Rössnerová, A., Ambrož, A., Šrám, R., Hajslová, J.: (2016) Relationship between atmospheric pollution in the residential area and concentrations of polycyclic aromatic hydrocarbons (PAHs) in human breast milk. Sci. Total Environ., 562:640-647. IN PRESS

Rossner, P., Orhan, H., Koppen, G., Sakai, K., Santella, R.M., Ambrož, A., Rossnerová, A., Šrám, R., Ciganek, M., Neca, J., Arzuk, E., Mutlu, N., Cooke, M.S.: (2016) Urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine analysis by an improved ELISA: An inter-laboratory comparison study. Free Radic. Biol. Med., 22;95: 169-179. IN PRESS

2014

Dostál, M., Průcha, M., Rychlíková, E., Pastorková, A., Šrám, R.: (2014) Differences between the spectra of respiratory illnesses in children living in urban and rural environments. Cent Eur J Public Health. 22(1): 3-11.

Líbalová, H., Krčková, S., Uhlířová, K., Milcová, A., Schmuczerová, J., Ciganek, M., Kléma, J., Machala, M., Šrám, R., Topinka, J.: (2014) Genotoxicity but not the AhR-mediated activity of PAHs is inhibited by other components of complex mixtures of ambient air pollutants. Toxicol Lett. 225(3): 350-357.

Líbalová H., Krčková, S., Uhlířová, K., Klema, J., Ciganek, M., Rössner, P. Jr., Šrám, R., Vondráček, J., Machala, M., Topinka, J.: (2014) Analysis of gene expression changes in A549 cells induced by organic compounds from respirable air particles. Mutat. Res.-Fundam. Mol. Mech. Mutagen. 770: 94-105.

McCullough, L. E., Santella, R. M., Cleveland, R. J., Millikan, R. C., Olshan, A. F., North, K. E., Bradshaw, P. T., Eng, S. M., Terry, M. B., Shen, J., Crew, K. D., Rössner, P. Jr., Teitelbaum, S. L., Neugut, A. I., Gammon, M.D.: (2014) Polymorphisms in DNA repair genes, recreational physical activity and breast cancer risk. Int. J. Cancer. 134(3): 654-663.

Průcha, M., Zazula, R., Herold, I., Dostál, M., Hyanek, T., Bellingan, G.: (2014) Presence of hypogammaglobulinemia in patients with severe sepsis, septic shock, and SIRS is associated with increased mortality. J. Infect. 68(3): 297-299.

Rössner, P., Jr, Rössnerová, A., Beskid, O., Tabashidze, N., Líbalová, H., Uhlířová, K., Topinka, J., Šrám, R.: (2014) Nonhomologous DNA end joining and chromosome aberrations in human embryonic lung fibroblasts treated with environmental pollutants. Mutat Res. (763-764): 28-38.

Sonnenschein-van der Voort, A. M., Arends, L. R., de Jongste, J. C., Annesi-Maesano, I., Arshad, S. H., Barros, H., Basterrechea, M., Bisgaard, H., Chatzi, L., Corpeleijn, E., Correia, S., Craig, L. C., Devereux, G., Dogaru, C., Dostál, M., Duchen, K., Eggesbø, M., van der Ent, C. K., Fantini, M. P., Forastiere, F., Frey, U., Gehring, U., Gori, D., van der Gugten, A. C., Hanke, W., Henderson, A. J., Heude, B., Iñiguez, C., Inskip, H. M., Keil, T., Kelleher, C. C., Kogevinas, M., Kreiner-Møller, E., Kuehni, C. E., Küpers, L. K., Lancz, K., Larsen, P. S., Lau, S., Ludvigsson, J., Mommers, M., Nybo Andersen, A. M., Palkovicova. L., Pike, K. C., Pizzi, C., Polanska, K., Porta, D., Richiardi, L., Roberts, G., Schmidt, A., Šrám, R., Sunyer, J., Thijs, C., Torrent, M., Viljoen, K., Wijga, A. H., Vrijheid, M., Jaddoe, V. W., Duijts, L.: (2014) Preterm birth, infant weight gain, and childhood asthma risk: A meta-analysis of 147,000 European children. J. Allergy Clin. Immunol. 133(5): 1317-1329.

Zablotskii, V., Lunov, O., Novotná, B., Churpita, O., Trošan, P., Holáň, V., Syková, E., Dejneka, A., Kubinová, Š.: (2014) Down-regulation of adipogenesis of mesenchymal stem cells by oscillating high-gradient magnetic fields and mechanical vibration.Appl. Phys. Lett. 105(10): 103702

White, A. J., Teitelbaum, S. L., Stellman, S. D., Beyea, J., Steck, S. E., Mordukhovich, I., McCarty, K. M., Ahn, J., Rössner, P., Jr, Santella, R. M., Gammon, M. D.: (2014) Indoor air pollution exposure from use of indoor stoves and fireplaces in association with breast cancer: a case-control study. Environ. Health. 13(1): 108.

2013

Barregård, L., Moller, P., Henriksen, T., Mistry, V., Koppen, G., Rössner, P. Jr., Šrám, R., Weimann, A., Poulsen, H., Nataf, R., Andreolli, R., Manini, P., Marczylo, T. H., Lam, P., Evans, M. D., Kasai, H., Kawai, K., Li, Y. S., Sakai, K., Singh, R., Teichert, F., Farmer, P., Rozalski, R., Gackowski, D., Siomek, A., Saez, G., Cerda, C., Broberg, K., Lund, C., Hossain, M., Haghdoost, S., Hu, C. W., Chao, M. R., Wu, K. Y., Senduran, N., Orhan, H., Smith, R. J., Santella, R., Su, Y., Cortez, C., Yeh, S., Olinski, R., Loft, S., Cooke, M.S.: (2012) Human and methodological sources of variability in the measurement of urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine. Antioxid. Redox Signal. 18(18): 2377-2391.

Bousquet, J. ... Šram, R. ... et al., (184 autorů): Pooling birth cohorts in allergy and asthma: European Union-funded initiatives - a MeDALL, CHICOS, ENRIECO, and GA²LEN joint paper. Int. Arch. Allergy. Immunol. 161(1): 1-10.

Dostál, M., Pastorková, A., Rychlik, S., Rychlikova, E., Švecová, V., Schallerová, E., Šrám, R.: (2013) Comparison of child morbidity in regions of Ostrava, Czech Republic, with different degrees of pollution: a retrospective cohort study. Environ. Health 12(1):74.

Fenech, M., Kirsch-Volders, M., Rössnerová, A., Šrám, R., Romm, H., Bolognes,i C., Ramakumar, A., Soussaline, F., Schunck, C., Elhajouji, A., Anwar, W., Bonassi, S.: (2013) HUMN project initiative and review of validation, quality control and prospects for further development of automated micronucleus assays using image cytometry systemsInt. J. Hyg. Environ. Health. 216(5): 541-552.

Ghosh, R., Topinka, J., Joad, J. P., Dostál, M., Šrám R., Hertz-Picciotto, I.: (2013) Air pollutants, genes and early childhood acute bronchitis. Mutat. Res.-Fundam. Mol. Mech. Mutagen. 749(1-2): 80-86.

Hyánková, L., Novotná, B.: (2013) Divergent selection for shape of growth curve in Japanese quail: 7. Effect of egg storage at high temperature on embryo development and hatchability. Br. Poult. Sci. 54(6): 695-703.

Larsen, P. S., Kamper-Jørgensen, M., Adamson, A., Barros, H., Bonde, J. P., Brescianini, S., Brophy, S., Casas, M., Devereux, G., Eggesbø, M., Fantini, M. P., Frey, U., Gehring, U., Grazuleviciene, R., Henriksen, T. B., Hertz-Picciotto, I., Heude, B., Hryhorczuk, D. O., Inskip, H., Jaddoe, V. W., Lawlor, D. A., Ludvigsson, J., Kelleher, C., Kiess, W., Koletzko, B., Kuehni, C. E., Kull, I., Kyhl, H. B., Magnus, P., Momas, I., Murray, D., Pekkanen, J., Polanska, K., Porta, D., Poulsen, G., Richiardi, L., Roeleveld, N., Skovgaard, A. M.,Šrám, R., Strandberg-Larsen, K., Thijs, C., Van Eijsden, M., Wright, J., Vrijheid, M., Andersen, A.M.: (2013) Pregnancy and birth cohort resources in europe: a large opportunity for aetiological child health research. Paediatr. Perinat. Epidemiol. 27(4): 393-414.

Pauk, N., Klimešová, S., Kara, J., Topinka, J., Labaj, J.: (2013) The relevance of monitoring of antibodies against the polycyclic aromatic hydrocarbon (PAH) and PAH-DNA adducts in serum in relation to lung cancer and chronic obstructive pulmonary disease (COPD). Neoplasma 60(2): 182-187.

Rössner, P. Jr., Mistry, V., Singh, R., Šrám, R., Cooke M. S.: (2013) Urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine values determined by a modified ELISA improves agreement with HPLC-MS/MS. Biochem. Biophys. Res. Commun. 440(4): 725-730.

Rössner, P. Jr., Mrhálková, A , Uhlířová, K., Špátová, M., Rössnerová, A., Líbalová, H., Schmuczerová, J., Milcová, A., Topinka. J., Šrám, R.: (2013) Nucleotide excision repair is not induced in human embryonic lung fibroblasts treated with environmental pollutants. PLoS One 8(7): e69197.

Rössner, P. Jr., Švecová,. V., Schmuczerová, J., Milcová, A., Tabashidze, N., Topinka, J., Pastorková, A., Šrám, R.: (2013) Analysis of biomarkers in a Czech population exposed to heavy air pollution. Part I. Bulky DNA adducts. Mutagenesis. 28(1): 89-95.

Rössner, P. Jr., Rössnerová, A., Špátová, M., Beskid, O., Uhlířová, K., Líbalová, H., Solanský, I., Topinka, J., Šrám, R.: (2013) Analysis of biomarkers in a Czech population exposed to heavy air pollution. Part II. Chromosomal aberrations and oxidative stress. Mutagenesis. 28(1): 97-106.

Rössnerová, A., Tulupová, E., Tabashidze, N., Schmuczerová, J., Dostál, M., Rössner, P. Jr., Gmuender, H., Šrám, R.: (2013) Factors affecting the 27K DNA methylation pattern in asthmatic and healthy children from locations with various environments.Mutat. Res.-Fundam. Mol. Mech. Mutagen. 741-742: 18-26.

Sedmíková, M., Petr, J., Dörflerová, A., Nevoral, J., Novotná, B., Krejčová, T., Chmelíková, E., Tůmová, L.: (2013) Inhibition of c-Jun N-terminal kinase (JNK) suppresses porcine oocyte ageing in vitro. Czech J. Anim. Sci., 58(12): 535-545.

Slama, R., Bottagisi, S., Solanský, I., Lepeule, J., Giorgis-Allemans, L., Šrám, R.: (2013) Short-term impact of atmospheric pollution on fecundability. Epidemiology. 24(6): 871-879.

Šmerdová, L., Neca, J., Svobodová, J., Topinka, J., Schmuczerová, J., Kozubík, A., Machala, M., Vondrácek, J.: (2013) Inflammatory mediators accelerate metabolism of benzo[a]pyrene in rat alveolar type II cells: the role of enhanced cytochrome P450 1B1 expression. Toxicology. 314: 30-38.

Šrám, R., Binková, B., Dostál, M., Merkerová-Dostalová, M., Líbalová, H., Milcová, A., Rössner, P. Jr., Rössnerová, A., Schmuczerová, J., Švecová, V., Topinka, J., Votavová, H.: (2013) Health impact of air pollution to children. Int. J. Hyg. Environ. Health. 216(5): 533-540.

Švecová, V., Topinka, J., Solanský, I., Rössner, P. Jr., Šrám, R.: (2013) Personal exposure to carcinogenic polycyclic aromatic hydrocarbons in the Czech Republic. J. Expos. Sci. Environ. Epidemiol. 23(4): 350-355.

Topinka, J., Milcová, A., Schmuczerová, J., Krouzek, J., Hovorka, J.: (2013) Ultrafine particles are not major carriers of carcinogenic PAHs and their genotoxicity in size-segregated aerosols. Mutat. Res. Genet. Toxicol. Environ. Mutagen. 754(1-2): 1-6..

Yauk, C. L., Bishop, J., Dearfield, K. L., Douglas, G. R., Hales, B. F., Luijten, M., O´Brien, J. M., Robaire, B., Šrám, R., van Bethem, J., Wade, M. G., White, P. A. Marchetti, F.: (2013) The development of adverse outcome pathways for mutagenic effects for the organization for economic co-operation and development. Environ. Mol. Mutagen. 54(2): 79-81.

2011-2016       MEDETOX - Innovative methods of monitoring of diesel engine exhaust toxicity in real urban traffic  (European Community, LIFE+, LIFE10 ENV/CZ/651)

2012-2018       CENATOX - Center for the Study of Toxic Properties of Nanoparticles (Czech Science Foundation, P503/12/G147)

2012-2016       CITI-SENSE - Development of sensor-based Citizens’ Observatory Community for improving quality of life in cities (FP7 EU project, FP7/ENV-2012-308524-2/CITI-SENSE)

2012- 2016      NANoREG - A common European approach to the regulatory testing of Manufactured Nanomaterials (FP7 EU project, Participant No.66, NANoREG)

2013-2016       NANOSTOX - Toxic effects of nanomaterials as a function of their structure and physico-chemical properties (Ministry of Education, Youth and Sports, COST.CZ LD 14002)

2013-2016       MODENA - Modelling of toxicity of nanomaterials (EU Cost Action TD 1204, MODENA)

2013-2016       G-NEW - Impact of air pollution to genome of newborns (Czech Science Foundation, 13-13458S)

2015-2020      NANOGEN - Genomics and Proteomics in the Study of Mechanisms of Biological Effects of Manufactured Nanoparticles (Ministry of Education, Youth and Sports, LO1508)

2015-2020      Nanoparticle Genotoxicity Measurement System (OPPK - Operational Program Prague Competitiveness, European Fund for Regional Development Prague & EU We invite you to your future, CZ.2.16/3.1.00/24507)

2016-2018      LIPITOX - Study of processes associated with lipid peroxidation in model human cell lines, (Czech Science Foundation, 16-14631S)

2016-2018      Strategie AV21-QUALITAS - research programme „Wellbeing in health and disease“  

2016- 2019      NanoEnviCz -Research Infrastructure (Ministry of Education, Youth and Sports, LM2015073)

2016- 2019      ProNanoEnviCz - Completion and Upgrading of RI Nanomaterials and Nanotechnologies for Environmental Protection and Sustainable Future (Ministry of Education, Youth and Sports)

2018-2020      MUCILTOX - Mechanisms of toxicity of emissions from petrol engines in 3D tissue cultures and in model bronchial epithelial cell line (Czech Science Foundation, 18-04719S)

2018-2020      GASODAM - Cellular Response Mechanisms of Organic Matter Genotoxicity in Petrol and Alternative Fuel Emissions on the Human Pulmonary Cell Model (Czech Science Foundation, 18-06548Y)

2018-2020      NANOEX - The effect of nanoparticle exposure on DNA changes in the human population (Czech Science Foundation, 18-02079S)

2018-2022      HAIE - Healthy Aging in Industrial Environment (European Union - European Structural and Investment Funds, Operational Program Research, Development and Education; Ministry of Education, Youth and Sports, CZ.02.1.01/0.0/0.0/16_019/0000798).

J. Heyrovský Institute of Physical Chemistry

Palacký University Olomouc

Technical University of Liberec

Jan Evangelista Purkyně University in Ústí nad Labem

Institute of Inorganic Chemistry

Veterinary Research Institute

Institute of Analytical Chemistry

Charles University in Prague

Institute of Chemical Process Fundamentals

Institute of Animal Physiology and Genetics

University of South Bohemia in České Budějovice

University of Chemistry and Technology, Prague

Research Centre for Toxic Compounds in the Environment, Brno


The National Institute of Occupational Health, Norway

Norwegian Institute for Air Research, Norway

Karolinska Institutet, Sweden

Institute of Occupational Medicine, Scotland

University of Manchester, UK

Flemish Institute for Technological Research, Belgium

University of Oslo, Norway

King’s College London, UK

Florida International University, MI, USA

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