The department deals with the study of the toxic effects of nanoparticles and fine particles produced in the air in human cell lines and in 3D lung models (MucilAirTM system). The impact of a polluted environment on humans is evaluated in molecular epidemiological studies. Research also focuses on stem cells and their role in the healing and regeneration of damaged tissues. The methods used include: determination of cytotoxicity, detection of oxidative damage of macromolecules (ELISA), changes in DNA integrity (comet assay, analysis of micronuclei and chromosomal aberrations), gene and protein expression (RT‑PCR, NGS, Western blotting), epigenetic parameters (miRNA, DNA methylation) and DNA repair.
Transcriptomic and epigenomic profiling reveals altered responses to diesel emissions in Alzheimer's disease both in vitro and in population-based data
Diesel exhaust (DE) exposure resulted in an almost four-fold higher response in Alzheimer disease olfactory mucosa cells, indicating increased susceptibility to DE effects. Methylation analysis detected different DNA methylation patterns, revealing new exposure targets. This study identifies air pollution exposure biomarkers and pinpoints key pathways activated by exposure. The data suggest that AD individuals may face heightened risks due to impaired cellular defenses.
Experimental study scheme. Olfactory mucosa cells from nasal biopsies of control and AD subjects were exposed to diesel exhaust emissions at air-liquid interface. Transcriptomic response as well as DNA methylation changes were analysed after exposure. Results were validated using a population-based Rotterdam study.
Publication:
Saveleva L, Červená T, Mengoni C et al. Transcriptomic and epigenomic profi ling reveals altered responses to diesel emissions in Alzheimer’s disease both in vitro and in population-based data. Alzheimer’s Dement. 2024;1-19. https://doi.org/10.1002/alz.14347
Effects of various environments on epigenetic settings and chromosomal damage
The study focused on the explanation of unexpected results obtained in a heavily polluted region of the Czech Republic (the lowest frequency of micronuclei related to highest concentrations of air pollutants). New results showed significantly lower frequencies of chromosomal breaks in this population, together with significantly lower DNA methylation profile in XRCC5 involved in the NHEJ repair pathway. The epigenetic adaptation was suggested as a reason for the reduced level of chromosomal breaks.
Examples of various types of micronuclei. Examples of cytochalasin B-blocked human peripheral blood lymphocytes stained with DAPI (blue) and pan-centromeric probes with FITC (green). (A): binucleated cell with a micronucleus with the presence of two centromere signals – chromosomal losses. (B): binucleated cell with a micronucleus with the absence of centromere signal – chromosomal break.
Publication:
Rossnerova, A.; Elzeinova, F.; Chvojkova, I.; Honkova, K.; Sima, M.; Milcova, A.; Pastorkova, A., Schmuczerova, J.; Rossner, P. Jr.; Topinka, J.; Sram, R.J. Effects of various environments on epigenetic settings and chromosomal damage. Environ. Pollut. 2023, 323, 121290. PMID: 36804881, DOI: 10.1016/j.envpol.2023.121290.
The impact of extractable organic matter from gasoline and alternative fuel emissions on bronchial cell models (BEAS-2B, MucilAir™)
Air pollution caused by road traffic has an unfavorable impact on the environment and also on human health. We focused on extractable organic matter (EOM) from particulate matter from fuels with different ethanol content. We performed cytotoxicity evaluation, quantification of mucin and extracellular reactive oxygen species production, DNA breaks detection, and selected gene deregulation analysis, after one and five days of exposure of human bronchial epithelial model (BEAS-2B) and a 3D model of the human airway (MucilAir™). Our data suggest that the longer exposure had more pronounced effects on the parameters of cytotoxicity and mucin production, while the impacts on ROS generation and DNA integrity were limited.
In MucilAir™ no significant differences were detected for E5 between 5-day and 1-day exposure, this EOM caused a differential expression of 13 genes in BEAS-2B cells. The expression of five and eight genes differed after exposure to E20 EOM in MucilAir™ or BEAS-2B cells, respectively, when the 5-day and 1-day treatment was compared.
Publication:
Šíma, M., Červená, T., Elzeinová, F., Ambrož, A., Beránek, V., Vojtíšek-Lom, M., Kléma, J., Ciganek, M., Rössner, P.: (2022) The impact of extractable organic matter from gasoline and alternative fuel emissions on bronchial cell models (BEAS-2B, MucilAir™). Toxicology in vitro. 80: 105316. doi: 10.1016/j.tiv.2022.105316. Epub 2022 Jan 21. PMID: 35066112.
Maternal Diet Quality and the Health Status of Newborns
The study evaluated the quality of the maternal diet and the health status of newborns. The results showed insufficient intake of vegetables, dairy products and fiber. The intake of the most persistent organic pollutants did not exceed limits, only the intake of perfluorinated substances exceeded the limit for 7.8% of women. Birth weight had a positive relationship with protein intake. Neonatal oxidative stress had a positive relationship with DDT intake and a negative relationship with protein intake.
Graphical abstract of the study and its results. First, the nutritional quality of the maternal diet was evaluated from the detailed food records (1) and chemical analysis of food samples contamination by persistent organic pollutants was performed (2). Subsequently, the relationships of these two factors with birth weight (3) and neonatal oxidative stress (4) were studied.
Publication:
Pavlíková, J., Ambrož, A., Hoňková, K., Chvojková, I., Šrám, R.J., Rössner, P., Topinka, J., Gramblička, T., Parizek, O., Parizkova, D., Pulcmanová, J., Rössnerová, A.: (2022) Maternal Diet Quality and Health Status of Newborns. Foods. 11(23): 3893.
Markers of lipid oxidation and inflammation in bronchial cells exposed to complete gasoline emissions and their organic extracts
We investigated the inflammation-related markers in human bronchial epithelial cells and a 3D model of the human airways after exposure to complete emissions and extractable organic matter from these emissions from two gasoline types. Exposure of the 3D model to emissions from ordinary gasoline induces a pro-inflammatory response. This observation highlights the potential negative impacts of ordinary gasoline, while the effects of an alternative fuel (with higher ethanol content) are relatively weak.
A comparison of production of immune response-relevant molecules by MucilAir™ and BEAS-2B cells exposed to complete emissions and EOMs from complete emissions from E5 and E20 fuels at time points T1 and T5. (A) Production of immune response-relevant molecules by MucilAir™ and BEAS-2B cells exposed to complete emissions from E5 and E20 fuels at time points T1 and T5. (B) Production of immune response-relevant molecules by MucilAir™ and BEAS-2B cells exposed to EOMs from complete emissions from E5 and E20 fuels at time points T1 and T5. Red and green colors denote increased and decreased levels of the respective marker, when compared with the control at the individual time point. ND, not detectable.
Publication:
Rössner, P., Červená, T., Vojtíšek-Lom, M., Neca, J., Ciganek, M., Vrbová, K., Ambrož, A., Nováková, Z., Elzeinová, F., Šíma, M., Šímová, Z., Holáň, V., Beránek, V., Pechout, M., Macoun, D., Rössnerová, A., Topinka, J.: (2021) Markers of lipid oxidation and inflammation in bronchial cells exposed to complete gasoline emissions and their organic extracts. Chemosphere. 281: 130833.
Individual DNA Methylation Pattern Shifts in Nanoparticle-Exposed Workers Analyzed in Four Consecutive Years
Our study focused on the impact of nanoparticle exposure on DNA methylation. We aimed to map methylation changes over time at the individual level for 4 years. The results showed fluctuation in methylation settings in both exposed and control persons. Overall, the changes were more pronounced in the exposed subjects, although for several CpG sites no modification was noted. These sites are linked with the process of adaptation, which is fixed by the process of the epigenetic memory.
Individual DNA methylation pattern trajectories. Examples of individual DNA methylation pattern trajectories of the nanoparticles exposed (#1 – #10) and control subjects (#11 – #14) analyzed by principal component analysis in four consecutive years (2016 – 2019): results of the whole CpG data set analyzed by 850K array chips.
Publication:
Rössnerová, A., Hoňková, K., Chvojková, I., Pelcová, D., Ždímal, V., Hubáček, J. A., Lischková, L., Vlčková, Š., Ondráček, J., Dvořáčková, Š., Topinka, J., Rössner, P.: (2021) Individual DNA Methylation Pattern Shifts in Nanoparticles-Exposed Workers Analyzed in Four Consecutive Years. International Journal of Molecular Sciences. 22(15): 7834. PMID: 34360600, PMCID: PMC8346047, doi: 10.3390/ijms22157834 (IF = 5.924).
Department of Toxicology and Molecular EpidemiologyGeorgieva N. I.Siegel E. R.Šrám R.Vacek P. M.Walker V. E.Albertini R. J.Swenberg J. A.Boysen G.
2025
Chem Res Toxicol . 2025 May 19;38(5):858-864. doi: 10.1021/acs.chemrestox.4c00530. Epub 2025 Apr 22.
Department of Toxicology and Molecular EpidemiologyOhtonen S.Jäntti H.Giudice L.Mohamed A.Shakirzyanova A.Závodná T.Belevich I.Yan H.Sabogal-Guáqueta A. M.Saveleva L.Väänänen M.-A.Rillo-Albert A.Perciballi E.Ferrari D.Tervo M.-M.Gómez-Budia M.Krejčík Z.Aakko-Saksa P.Koistinaho J.Lehtonen Š.Kanninen K. M.Topinka J.Jokitalo E.Sierra A.Schmidt M.Dolga A. M.Jalava P. I.Korhonen P.Malm T.
2025
Environ Int . 2025 May:199:109467. doi: 10.1016/j.envint.2025.109467. Epub 2025 May 5.
Department of Toxicology and Molecular EpidemiologyLintusaari H.Lepistö T.Saarikoski S.Salo L.Silvonen V.Barreira L. M. F.Aurela M.Hoivala J.Markkula L.Ondracek J.Wahle T.Vojtíšek M.Topinka J.Schins R. P. F.Jalava P.Timonen H.Kanninen K. M.Rönkkö T.
2025
Environ Pollut . 2025 Mar 15:369:125835. doi: 10.1016/j.envpol.2025.125835. Epub 2025 Feb 11.
Department of Toxicology and Molecular EpidemiologyMussalo L.Avesani S.Shahbaz M. A.Závodná T.Saveleva L.Järvinen A.Lampinen R.Belaya I.Krejčík Z.Ivanova M.Hakkarainen H.Kalapudas J.Penttilä E.Löppönen H.Koivisto A. M.Malm T.Topinka J.Giugno R.Aakko-Saksa P.Chew S.Rönkkö T.Jalava P.Kanninen K. M.
2023
Sci Total Environ. 2023 Dec 20:905:167038. doi: 10.1016/j.scitotenv.2023.167038. Epub 2023 Sep 13.
Department of Toxicology and Molecular EpidemiologySilvonen V.Salo L.Raunima T.Vojtisek-Lom M.Ondracek J.Topinka J.Schins R. P. F.Lepistö T.Lintusaari H.Saarikoski S.Barreira L. M. F.Hoivala J.Markkula L.Kulmala IVinha J.Karjalainen P.Rönkkö T.
2023
Building and Environment. 246: 110999. Volume 246, 1 December 2023, https://doi.org/10.1016/j.buildenv.2023.110999
Department of Toxicology and Molecular EpidemiologyLepistö T.Lintusaari H.Oudin A.Barreira L. M. F.Niemi J. V.Karjalainen P.Salo L.Silvonen V.Markkula L.Hoivala J.Marjanen P.Martikainen S.Aurela M.Reyes F. R.Oyola P.Kuuluvainen H.Manninen H. E.Schins R. P. F.Vojtisek-Lom M.Ondracek J.Topinka J.Timonen H.Jalava P.Saarikoski S.Rönkkö T.
2023
Environ Int. 2023 Oct:180:108224. doi: 10.1016/j.envint.2023.108224. Epub 2023 Sep 20.
Department of Toxicology and Molecular EpidemiologyMartikainen M.V.Aakko-Saksa P.van den Broek L.Flemming R.C.Carare R.O.Chew S.Dinnyes A.Giugno R.Kanninen K.M.Malm T.Muala A.Nedergaard M.Oudin A.Oyola P.Pfeiffer T.V.Ronkko T.Sandstrom T.Schins R.P.F.Topinka J.Yang M.Zeng X.Westerink R.H.S.Jalava P.I.
2022
International Journal of Environmental Research and Public Health. 19(1): 311.
Department of Toxicology and Molecular EpidemiologyPřichystalová R.Caron-Beaudoin E.Richardson l.Dirkx E.Amadou A.Závodná T.Cihak R.Cogliano V.Hynes J.Pelland-St-Pierre L.Verner M.A.van Tongeren M.Ho V.
2021
Journal of Exposure Science and Environmental Epidemiology. 07/20.
Department of Toxicology and Molecular EpidemiologyJandacka D.Uchytil J.Zahradnik D.Farana R.Vilimek D.Skypala J.Urbaczka J.Plesek J.Motyka A.Blaschova D.Beinhauerova G.Rygelova M.Brtva P.Balazova K.Horka V.Malus J.Freedman Silvernail J.Irwin G.Nieminen M.T.Casula V.Juras V.Golian M.Elavsky S.Knapova L.Šrám R.Hamill J.
2020
International Journal of Environmental Research and Public Health. 17(23): 9142.
2025
Atmospheric Environment: X Volume 28, December 2025, 100375 https://doi.org/10.1016/j.aeaoa.2025.100375
