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 CYP1A1 and GSTA3 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.

Centre of Vehicles for Sustainable Mobility Faculty of Mechanical Engineering Czech Technical University Prague Technicka 4 160 00 Prague Czech Republic

Department of Chemistry and Toxicology Veterinary Research Institute 621 00 Brno Czech Republic

Department of Computer Science Czech Technical University Prague 121 35 Prague Czech Republic

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

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

Department of Physiology Faculty of Science Charles University Vinicna 7 128 44 Prague Czech Republic

Department of Vehicles and Ground Transport Czech University of Life Sciences Prague Kamycka 129 165 21 Prague Czech Republic

Zobrazit více v PubMed

Sram R.J., Binkova B., Dejmek J., Bobak M. Ambient Air Pollution and Pregnancy Outcomes: A Review of the Literature. Environ. Health Perspect. 2005;113:375–382. doi: 10.1289/ehp.6362. PubMed DOI PMC

Sram R.J., Binkova B., Rössner P., Rubes J., Topinka J., Dejmek J. Adverse Reproductive Outcomes from Exposure to Environmental Mutagens. Mutat. Res. Fundam. Mol. Mech. Mutagen. 1999;428:203–215. doi: 10.1016/S1383-5742(99)00048-4. PubMed DOI

LEWTAS J. Air Pollution Combustion Emissions: Characterization of Causative Agents and Mechanisms Associated with Cancer, Reproductive, and Cardiovascular Effects. Mutat. Res. Mutat. Res. 2007;636:95–133. doi: 10.1016/j.mrrev.2007.08.003. PubMed DOI

IARC . Diesel Engine Exhaust Carcinogenic. IARC; Lyon, France: 2012. Press Release N° 213. PubMed

IARC Monographs . Diesel and Gasoline Engine Exhausts. Volume 105 IARC Monographs; Lyon, France: 2014.

Möhner M. Driving Ban for Diesel-Powered Vehicles in Major Cities: An Appropriate Penalty for Exceeding the Limit Value for Nitrogen Dioxide? Int. Arch. Occup. Environ. Health. 2018;91:373–376. doi: 10.1007/s00420-018-1297-4. PubMed DOI PMC

Yang J., Roth P., Ruehl C.R., Shafer M.M., Antkiewicz D.S., Durbin T.D., Cocker D., Asa-Awuku A., Karavalakis G. Physical, Chemical, and Toxicological Characteristics of Particulate Emissions from Current Technology Gasoline Direct Injection Vehicles. Sci. Total Environ. 2019;650:1182–1194. doi: 10.1016/j.scitotenv.2018.09.110. PubMed DOI

DeMarini D.M. Genotoxicity Biomarkers Associated with Exposure to Traffic and Near-Road Atmospheres: A Review. Mutagenesis. 2013;28:485–505. doi: 10.1093/mutage/get042. PubMed DOI

Oldham M.J., Castro N., Zhang J., Rostami A., Lucci F., Pithawalla Y., Kuczaj A.K., Gilman I.G., Kosachevsky P., Hoeng J., et al. Deposition Efficiency and Uniformity of Monodisperse Solid Particle Deposition in the Vitrocell® 24/48 Air–Liquid-Interface in Vitro Exposure System. Aerosol Sci. Technol. 2020;54:52–65. doi: 10.1080/02786826.2019.1676877. PubMed DOI

Chan J.H., Tsolakis A., Herreros J.M., Kallis K.X., Hergueta C., Sittichompoo S., Bogarra M. Combustion, Gaseous Emissions and PM Characteristics of Di-Methyl Carbonate (DMC)-Gasoline Blend on Gasoline Direct Injection (GDI) Engine. Fuel. 2020;263:116742. doi: 10.1016/j.fuel.2019.116742. DOI

Yang J., Roth P., Durbin T.D., Shafer M.M., Hemming J., Antkiewicz D.S., Asa-Awuku A., Karavalakis G. Emissions from a Flex Fuel GDI Vehicle Operating on Ethanol Fuels Show Marked Contrasts in Chemical, Physical and Toxicological Characteristics as a Function of Ethanol Content. Sci. Total Environ. 2019;683:749–761. doi: 10.1016/j.scitotenv.2019.05.279. PubMed DOI

Carugno M., Consonni D., Randi G., Catelan D., Grisotto L., Bertazzi P.A., Biggeri A., Baccini M. Air Pollution Exposure, Cause-Specific Deaths and Hospitalizations in a Highly Polluted Italian Region. Environ. Res. 2016;147:415–424. doi: 10.1016/j.envres.2016.03.003. PubMed DOI

Luyts K., Napierska D., Dinsdale D., Klein S.G., Serchi T., Hoet P.H.M. A Coculture Model of the Lung-Blood Barrier: The Role of Activated Phagocytic Cells. Toxicol. Vitr. 2014;29:234–241. doi: 10.1016/j.tiv.2014.10.024. PubMed DOI

Shah U.K., de Mallia J.O., Singh N., Chapman K.E., Doak S.H., Jenkins G.J.S. A Three-Dimensional in Vitro HepG2 Cells Liver Spheroid Model for Genotoxicity Studies. Mutat. Res. Genet. Toxicol. Environ. Mutagen. 2018;825:51–58. doi: 10.1016/j.mrgentox.2017.12.005. PubMed DOI

Furubayashi T., Inoue D., Nishiyama N., Tanaka A., Yutani R., Kimura S., Katsumi H., Yamamoto A., Sakane T. Comparison of Various Cell Lines and Three-Dimensional Mucociliary Tissue Model Systems to Estimate Drug Permeability Using an In Vitro Transport Study to Predict Nasal Drug Absorption in Rats. Pharmaceutics. 2020;12:79. doi: 10.3390/pharmaceutics12010079. PubMed DOI PMC

Ridley C., Thornton D.J. Mucins: The Frontline Defence of the Lung. Biochem. Soc. Trans. 2018;46:1099–1106. doi: 10.1042/BST20170402. PubMed DOI PMC

Tratnjek L., Kreft M., Kristan K., Kreft M.E. Ciliary Beat Frequency of in Vitro Human Nasal Epithelium Measured with the Simple High-Speed Microscopy Is Applicable for Safety Studies of Nasal Drug Formulations. Toxicol. Vitr. 2020;66:104865. doi: 10.1016/j.tiv.2020.104865. PubMed DOI

Loiseau E., Gsell S., Nommick A., Jomard C., Gras D., Chanez P., D’Ortona U., Kodjabachian L., Favier J., Viallat A. Active Mucus–Cilia Hydrodynamic Coupling Drives Self-Organization of Human Bronchial Epithelium. Nat. Phys. 2020 doi: 10.1038/s41567-020-0980-z. DOI

Arora P., Sharma S., Garg S. Permeability Issues in Nasal Drug Delivery. Drug Discov. Today. 2002;7:967–975. doi: 10.1016/S1359-6446(02)02452-2. PubMed DOI

Mercier C., Jacqueroux E., He Z., Hodin S., Constant S., Perek N., Boudard D., Delavenne X. Pharmacological Characterization of the 3D MucilAirTM Nasal Model. Eur. J. Pharm. Biopharm. 2019;139:186–196. doi: 10.1016/j.ejpb.2019.04.002. PubMed DOI

Kletting S., Barthold S., Repnik U., Griffiths G., Loretz B., Schneider-Daum N., de Carvalho-Wodarz C.S., Lehr C.-M.M. Co-Culture of Human Alveolar Epithelial (HAELVi) and Macrophage (THP-1) Cell Lines. ALTEX. 2018;35:211–222. doi: 10.14573/altex.1607191. PubMed DOI

Huang S., Wiszniewski L., Constant S., Roggen E. Potential of in Vitro Reconstituted 3D Human Airway Epithelia (MucilAirTM) to Assess Respiratory Sensitizers. Toxicol. Vitr. 2013;27:1151–1156. doi: 10.1016/j.tiv.2012.10.010. PubMed DOI

Huang S., Boda B., Vernaz J., Ferreira E., Wiszniewski L., Constant S. Establishment and Characterization of an in Vitro Human Small Airway Model (SmallAir TM ) Eur. J. Pharm. Biopharm. 2017 doi: 10.1016/j.ejpb.2016.12.006. PubMed DOI

Balharry D., Sexton K., Bérubé K.A. An in Vitro Approach to Assess the Toxicity of Inhaled Tobacco Smoke Components: Nicotine, Cadmium, Formaldehyde and Urethane. Toxicology. 2008;244:66–76. doi: 10.1016/j.tox.2007.11.001. PubMed DOI

Müller L., Comte P., Czerwinski J., Kasper M., Mayer A.C.R., Gehr P., Burtscher H., Morin J.-P., Konstandopoulos A., Rothen-Rutishauser B. New Exposure System To Evaluate the Toxicity of (Scooter) Exhaust Emissions in Lung Cells in Vitro. Environ. Sci. Technol. 2010;44:2632–2638. doi: 10.1021/es903146g. PubMed DOI

Steiner S., Mueller L., Popovicheva O.B., Raemy D.O., Czerwinski J., Comte P., Mayer A., Gehr P., Rothen-Rutishauser B., Clift M.J.D. Cerium Dioxide Nanoparticles Can Interfere with the Associated Cellular Mechanistic Response to Diesel Exhaust Exposure. Toxicol. Lett. 2012;214:218–225. doi: 10.1016/j.toxlet.2012.08.026. PubMed DOI

Hawley B., L’Orange C., Olsen D.B., Marchese A.J., Volckens J. Oxidative Stress and Aromatic Hydrocarbon Response of Human Bronchial Epithelial Cells Exposed to Petro- or Biodiesel Exhaust Treated with a Diesel Particulate Filter. Toxicol. Sci. 2014;141:505–514. doi: 10.1093/toxsci/kfu147. PubMed DOI PMC

Jonsdottir H.R., Delaval M., Leni Z., Keller A., Brem B.T., Siegerist F., Schönenberger D., Durdina L., Elser M., Burtscher H., et al. Non-Volatile Particle Emissions from Aircraft Turbine Engines at Ground-Idle Induce Oxidative Stress in Bronchial Cells. Commun. Biol. 2019;2:90. doi: 10.1038/s42003-019-0332-7. PubMed DOI PMC

Ghio A.J., Dailey L.A., Soukup J.M., Stonehuerner J., Richards J.H., Devlin R.B. Growth of Human Bronchial Epithelial Cells at an Air-Liquid Interface Alters the Response to Particle Exposure. Part. Fibre Toxicol. 2013;10:1. doi: 10.1186/1743-8977-10-25. PubMed DOI PMC

Totlandsdal A.I., Låg M., Lilleaas E., Cassee F., Schwarze P. Differential Proinflammatory Responses Induced by Diesel Exhaust Particles with Contrasting PAH and Metal Content. Environ. Toxicol. 2015;30:188–196. doi: 10.1002/tox.21884. PubMed DOI

Goudarzi G., Shirmardi M., Naimabadi A., Ghadiri A., Sajedifar J. Chemical and Organic Characteristics of PM2.5 Particles and Their in-Vitro Cytotoxic Effects on Lung Cells: The Middle East Dust Storms in Ahvaz, Iran. Sci. Total Environ. 2019;655:434–445. doi: 10.1016/j.scitotenv.2018.11.153. PubMed DOI

Libalova H., Rossner P., Vrbova K., Brzicova T., Sikorova J., Vojtisek-Lom M., Beranek V., Klema J., Ciganek M., Neca J., et al. Transcriptional Response to Organic Compounds from Diverse Gasoline and Biogasoline Fuel Emissions in Human Lung Cells. Toxicol. Vitr. 2018;48:329–341. doi: 10.1016/j.tiv.2018.02.002. PubMed DOI

Velali E., Papachristou E., Pantazaki A., Choli-Papadopoulou T., Argyrou N., Tsourouktsoglou T., Lialiaris S., Constantinidis A., Lykidis D., Lialiaris T.S., et al. Cytotoxicity and Genotoxicity Induced in Vitro by Solvent-Extractable Organic Matter of Size-Segregated Urban Particulate Matter. Environ. Pollut. 2016;218:1350–1362. doi: 10.1016/j.envpol.2016.09.001. PubMed DOI

Velali E., Papachristou E., Pantazaki A., Choli-Papadopoulou T., Planou S., Kouras A., Manoli E., Besis A., Voutsa D., Samara C. Redox Activity and in Vitro Bioactivity of the Water-Soluble Fraction of Urban Particulate Matter in Relation to Particle Size and Chemical Composition. Environ. Pollut. 2016;208:774–786. doi: 10.1016/j.envpol.2015.10.058. PubMed DOI

Vojtisek-Lom M., Pechout M., Macoun D., Rameswaran R., Praharaj K.K., Cervena T., Topinka J., Rossner P. Assessing Exhaust Toxicity with Biological Detector: Configuration of Portable Air-Liquid Interface Human Lung Cell Model Exposure System, Sampling Train and Test Conditions. SAE Int. J. Adv. Curr. Pract. Mobil. 2019 doi: 10.4271/2019-24-0050. DOI

Steiner S., Czerwinski J., Comte P., Heeb N.V., Mayer A., Petri-Fink A., Rothen-Rutishauser B. Effects of an Iron-Based Fuel-Borne Catalyst and a Diesel Particle Filter on Exhaust Toxicity in Lung Cells in Vitro. Anal. Bioanal. Chem. 2015;407:5977–5986. doi: 10.1007/s00216-014-7878-5. PubMed DOI

Bisig C., Comte P., Güdel M., Czerwinski J., Mayer A., Müller L., Petri-Fink A., Rothen-Rutishauser B. Assessment of Lung Cell Toxicity of Various Gasoline Engine Exhausts Using a Versatile in Vitro Exposure System. Environ. Pollut. 2018;235:263–271. doi: 10.1016/j.envpol.2017.12.061. PubMed DOI

Bisig C., Roth M., Müller L., Comte P., Heeb N., Mayer A., Czerwinski J., Petri-Fink A., Rothen-Rutishauser B. Hazard Identification of Exhausts from Gasoline-Ethanol Fuel Blends Using a Multi-Cellular Human Lung Model. Environ. Res. 2016;151:789–796. doi: 10.1016/j.envres.2016.09.010. PubMed DOI

Aufderheide M., Scheffler S., Ito S., Ishikawa S., Emura M. Ciliatoxicity in Human Primary Bronchiolar Epithelial Cells after Repeated Exposure at the Air–Liquid Interface with Native Mainstream Smoke of K3R4F Cigarettes with and without Charcoal Filter. Exp. Toxicol. Pathol. 2015;67:407–411. doi: 10.1016/j.etp.2015.04.006. PubMed DOI

Chortarea S., Clift M.J.D., Vanhecke D., Endes C., Wick P., Petri-Fink A., Rothen-Rutishauser B. Repeated Exposure to Carbon Nanotube-Based Aerosols Does Not Affect the Functional Properties of a 3D Human Epithelial Airway Model. Nanotoxicology. 2015;5390:1–11. doi: 10.3109/17435390.2014.993344. PubMed DOI

Méausoone C., El Khawaja R., Tremolet G., Siffert S., Cousin R., Cazier F., Billet S., Courcot D., Landkocz Y. In Vitro Toxicological Evaluation of Emissions from Catalytic Oxidation Removal of Industrial VOCs by Air/Liquid Interface (ALI) Exposure System in Repeated Mode. Toxicol. Vitr. 2019;58:110–117. doi: 10.1016/j.tiv.2019.03.030. PubMed DOI

Ito S., Matsumura K., Ishimori K., Ishikawa S. In Vitro Long-term Repeated Exposure and Exposure Switching of a Novel Tobacco Vapor Product in a Human Organotypic Culture of Bronchial Epithelial Cells. J. Appl. Toxicol. 2020;40:1248–1258. doi: 10.1002/jat.3982. PubMed DOI PMC

Di Cristo L., Grimaldi B., Catelani T., Vázquez E., Pompa P.P., Sabella S. Repeated Exposure to Aerosolized Graphene Oxide Mediates Autophagy Inhibition and Inflammation in a Three-Dimensional Human Airway Model. Mater. Today Bio. 2020;6 doi: 10.1016/j.mtbio.2020.100050. PubMed DOI PMC

Ishikawa S., Matsumura K., Kitamura N., Takanami Y., Ito S. Multi-Omics Analysis: Repeated Exposure of a 3D Bronchial Tissue Culture to Whole-Cigarette Smoke. Toxicol. Vitr. 2019;54:251–262. doi: 10.1016/j.tiv.2018.10.001. PubMed DOI

Svecova V., Topinka J., Solansky I., Rossner P., Sram R.J. Personal Exposure to Carcinogenic Polycyclic Aromatic Hydrocarbons in the Czech Republic. J. Expo. Sci. Environ. Epidemiol. 2013;23:350–355. doi: 10.1038/jes.2012.110. PubMed DOI

Good N., Mölter A., Ackerson C., Bachand A., Carpenter T., Clark M.L., Fedak K.M., Kayne A., Koehler K., Moore B., et al. The Fort Collins Commuter Study: Impact of Route Type and Transport Mode on Personal Exposure to Multiple Air Pollutants. J. Expo. Sci. Environ. Epidemiol. 2016;26:397–404. doi: 10.1038/jes.2015.68. PubMed DOI PMC

Campen M., Robertson S., Lund A., Lucero J., McDonald J. Engine Exhaust Particulate and Gas Phase Contributions to Vascular Toxicity. Inhal. Toxicol. 2014;26:353–360. doi: 10.3109/08958378.2014.897776. PubMed DOI PMC

Kooter I.M., Alblas M.J., Jedynska A.D., Steenhof M., Houtzager M.M.G., Van Ras M. Alveolar Epithelial Cells (A549) Exposed at the Air–Liquid Interface to Diesel Exhaust: First Study in TNO’s Powertrain Test Center. Toxicol. Vitr. 2013;27:2342–2349. doi: 10.1016/j.tiv.2013.10.007. PubMed DOI

Cao X., Muskhelishvili L., Latendresse J., Richter P., Heflich R.H. Evaluating the Toxicity of Cigarette Whole Smoke Solutions in an Air-Liquid-Interface Human in Vitro Airway Tissue Model. Toxicol. Sci. 2017;1156:14–24. doi: 10.1093/toxsci/kfw239. PubMed DOI

Reddel R.R., Ke Y., Gerwin B.I., McMenamin M.G., Lechner J.F., Su R.T., Brash D.E., Park J.B., Rhim J.S., Harris C.C. Transformation of Human Bronchial Epithelial Cells by Infection with SV40 or Adenovirus-12 SV40 Hybrid Virus, or Transfection via Strontium Phosphate Coprecipitation with a Plasmid Containing SV40 Early Region Genes. Cancer Res. 1988;48:1904–1909. PubMed

Rossner P., Cervena T., Vojtisek-Lom M., Vrbova K., Ambroz A., Novakova Z., Elzeinova F., Margaryan H., Beranek V., Pechout M., et al. The Biological Effects of Complete Gasoline Engine Emissions Exposure in a 3D Human Airway Model (MucilAirTM) and in Human Bronchial Epithelial Cells (BEAS-2B) Int. J. Mol. Sci. 2019;20:5710. doi: 10.3390/ijms20225710. PubMed DOI PMC

Benson K., Cramer S., Galla H.J. Impedance-Based Cell Monitoring: Barrier Properties and Beyond. Fluids Barriers CNS. 2013;10:1–11. doi: 10.1186/2045-8118-10-5. PubMed DOI PMC

Nalayanda D.D., Fulton W.B., Colombani P.M., Wang T.H., Abdullah F. Pressure Induced Lung Injury in a Novel in Vitro Model of the Alveolar Interface: Protective Effect of Dexamethasone. J. Pediatr. Surg. 2014;49:61–65. doi: 10.1016/j.jpedsurg.2013.09.030. PubMed DOI

Piao M.J., Ahn M.J., Kang K.A., Ryu Y.S., Hyun Y.J., Shilnikova K., Zhen A.X., Jeong J.W., Choi Y.H., Kang H.K., et al. Particulate Matter 2.5 Damages Skin Cells by Inducing Oxidative Stress, Subcellular Organelle Dysfunction, and Apoptosis. Arch. Toxicol. 2018;92:2077–2091. doi: 10.1007/s00204-018-2197-9. PubMed DOI PMC

Watterson T.L., Hamilton B., Martin R., Coulombe R.A. Urban Particulate Matter Causes ER Stress and the Unfolded Protein Response in Human Lung Cells. Toxicol. Sci. 2009;112:111–122. doi: 10.1093/toxsci/kfp186. PubMed DOI

Trieu D., Waddell T.K., McGuigan A.P. A Microfluidic Device to Apply Shear Stresses to Polarizing Ciliated Airway Epithelium Using Air Flow. Biomicrofluidics. 2014;8:1–14. doi: 10.1063/1.4901930. PubMed DOI PMC

Garcia-Canton C., Anadón A., Meredith C. ΓH2AX as a Novel Endpoint to Detect DNA Damage: Applications for the Assessment of the in Vitro Genotoxicity of Cigarette Smoke. Toxicol. Vitr. 2012;26:1075–1086. doi: 10.1016/j.tiv.2012.06.006. PubMed DOI

Audebert M., Riu A., Jacques C., Hillenweck A., Jamin E.L., Zalko D., Cravedi J.P. Use of the ΓH2AX Assay for Assessing the Genotoxicity of Polycyclic Aromatic Hydrocarbons in Human Cell Lines. Toxicol. Lett. 2010;199:182–192. doi: 10.1016/j.toxlet.2010.08.022. PubMed DOI

Oya E., Ovrevik J., Arlt V.M., Nagy E., Phillips D.H., Holme J.A. DNA Damage and DNA Damage Response in Human Bronchial Epithelial BEAS-2B Cells Following Exposure to 2-Nitrobenzanthrone and 3-Nitrobenzanthrone: Role in Apoptosis. Mutagenesis. 2011;26:697–708. doi: 10.1093/mutage/ger035. PubMed DOI

Rossner P., Rossnerova A., Beskid O., Tabashidze N., Libalova H., Uhlirova K., Topinka J., Sram R.J. Nonhomologous DNA End Joining and Chromosome Aberrations in Human Embryonic Lung Fibroblasts Treated with Environmental Pollutants. Mutat. Res. Fundam. Mol. Mech. Mutagen. 2014;763–764:28–38. doi: 10.1016/j.mrfmmm.2014.03.006. PubMed DOI

Toyooka T., Shinmen T., Aarts J.M.M.J.G., Ibuki Y. Dual Effects of N-Acetyl-l-Cysteine Dependent on NQO1 Activity: Suppressive or Promotive of 9,10-Phenanthrenequinone-Induced Toxicity. Toxicol. Appl. Pharmacol. 2012;264:404–412. doi: 10.1016/j.taap.2012.08.017. PubMed DOI

Yamamori T., Meike S., Nagane M., Yasui H., Inanami O. ER Stress Suppresses DNA Double-Strand Break Repair and Sensitizes Tumor Cells to Ionizing Radiation by Stimulating Proteasomal Degradation of Rad51. FEBS Lett. 2013;587:3348–3353. doi: 10.1016/j.febslet.2013.08.030. PubMed DOI

Tomašek I., Horwell C.J., Bisig C., Damby D.E., Comte P., Czerwinski J., Petri-Fink A., Clift M.J.D., Drasler B., Rothen-Rutishauser B. Respiratory Hazard Assessment of Combined Exposure to Complete Gasoline Exhaust and Respirable Volcanic Ash in a Multicellular Human Lung Model at the Air-Liquid Interface. Environ. Pollut. 2018;238:977–987. doi: 10.1016/j.envpol.2018.01.115. PubMed DOI

Cervena T., Vrbova K., Rossnerova A., Topinka J., Rossner P. Short-Term and Long-Term Exposure of the MucilAirTM Model to Polycyclic Aromatic Hydrocarbons. Altern. Lab. Anim. 2019;47:9–18. doi: 10.1177/0261192919841484. PubMed DOI

Ke S., Rabson A.B., Germino J.F., Gallo M.A., Tian Y. Mechanism of Suppression of Cytochrome P-450 1A1 Expression by Tumor Necrosis Factor-α and Lipopolysaccharide. J. Biol. Chem. 2001;276:39638–39644. doi: 10.1074/jbc.M106286200. PubMed DOI

Omura S., Koike E., Kobayashi T. Microarray Analysis of Gene Expression in Rat Alveolar Epithelial Cells Exposed to Fractionated Organic Extracts of Diesel Exhaust Particles. Toxicology. 2009;262:65–72. doi: 10.1016/j.tox.2009.05.012. PubMed DOI

Ewels P., Peltzer A., Fillinger S., Alneberg J., Patel H., Wilm A., Garcia M.U., Di Tommaso P., Nahnsen S. Nf-Core: Community Curated Bioinformatics Pipelines. bioRxiv. 2019:610741. doi: 10.1038/s41587-020-0439-x. PubMed DOI

Love M.I., Huber W., Anders S. Moderated Estimation of Fold Change and Dispersion for RNA-Seq Data with DESeq2. Genome Biol. 2014;15:550. doi: 10.1186/s13059-014-0550-8. PubMed DOI PMC

Chen J., Bardes E.E., Aronow B.J., Jegga A.G. ToppGene Suite for gene list enrichment analysis and candidate gene prioritization. Nucleic Acids Research. 2009;37:W305–W311. doi: 10.1093/nar/gkp427. PubMed DOI PMC

Transcriptomic and epigenomic profiling reveals altered responses to diesel emissions in Alzheimer's disease both in vitro and in population-based data