Gene expression profiling of A549 cells exposed to Milan PM2.5
Abstract
Background Particulate matter (PM) has been associated to adverse health effects in exposed population and DNA damage has been extensively reported in in vitro systems exposed to fine PM (PM2.5). The ability to induce gene expression profile modulation, production of reactive oxygen species (ROS) and strand breaks to DNA molecules has been investigated in A549 cells exposed to winter and summer Milan PM2.5.Results A549 cells, exposed to 10 μg/cm(2) of both winter and summer PM2.5, showed increased cytotoxicity at 24h and a significant increase of ROS at 3h of treatment. Despite these similar effects winter PM induced a higher number of gene modulation in comparison with summer PM. Both PMs modulated genes related to the response to xenobiotic stimuli (CYP1A1, CYP1B1, TIPARP, ALDH1A3, AHRR) and to the cell-cell signalling (GREM1) pathways with winter PM2.5 inducing higher fold increases. Moreover the winter fraction modulated also JUN (cell-cell signalling), GDF15, SIPA1L2 (signal transduction), and HMOX1 (oxidative stress). Two genes, epiregulin (EREG) and FOS-like antigen1 (FOSL1), were significantly up-regulated by summer PM2.5. The results obtained with the microarray approach have been confirmed by qPCR and by the analysis of CYP1B1 expression. Comet assay evidenced that winter PM2.5 induced more DNA strand breaks than the summer one.Conclusion Winter PM2.5 is able to induce gene expression alteration, ROS production and DNA damage. These effects are likely to be related to the CYP enzyme activation in response to the polycyclic aromatic hydrocarbons (PAHs) adsorbed on particle surface.
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Oxidative stress is a common mechanism of PM2.5-induced damage.
“Accumulated evidence indicates that oxidative stress is a common mechanism of PM2.5-induced damage (Gualtieri et al. 2012; Kouassi et al. 2010).”
From Particulate matter 2.5 damages skin cells by inducing oxidative stress, subcellular organelle dysfunction, and apoptosis (2018) · cites this paper as Gualtieri et al. 2012
Cites
Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources
Huang, D. W., Sherman, B. T., & Lempicki, R. A. (2009) · Nature Protocols · doi:10.1038/nprot.2008.211 · Cited by 35,890 · see citing works
Exploration, normalization, and summaries of high density oligonucleotide array probe level data
Irizarry, R. A. (2003) · Biostatistics · doi:10.1093/biostatistics/4.2.249 · Cited by 10,603 · see citing works
Fine-Particulate Air Pollution and Life Expectancy in the United States
Pope, C. A., Ezzati, M., & Dockery, D. W. (2009) · New England Journal of Medicine · doi:10.1056/nejmsa0805646 · Cited by 2,222 · see citing works
Oxidative stress-induced DNA damage by particulate air pollution
Risom, L., Möller, P., & Loft, S. H. (2005) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2005.06.012 · Cited by 914 · see citing works
Fine particles and human health—a review of epidemiological studies
Englert, N. (2004) · Toxicology Letters · doi:10.1016/j.toxlet.2003.12.035 · Cited by 674 · see citing works
The Effect of Fine and Coarse Particulate Air Pollution on Mortality: A National Analysis
Zanobetti, A., & Schwartz, J. D. (2009) · Environmental Health Perspectives · doi:10.1289/ehp.0800108 · Cited by 642 · see citing works
Characterisation of PM10 and PM2.5 particulate matter in the ambient air of Milan (Italy)
Marcazzan, G. M. B., Vaccaro, S., Valli, G., & Vecchi, R. (2001) · Atmospheric Environment · doi:10.1016/s1352-2310(01)00124-8 · Cited by 515 · see citing works
SiO2 nanoparticles induce cytotoxicity and protein expression alteration in HaCaT cells
Yang, X., Liu, J., He, H., Zhou, L., Gong, C., Wang, X., Yang, L., Yuan, J., Huang, H., He, L., et al. (2010) · Particle and Fibre Toxicology · doi:10.1186/1743-8977-7-1 · Cited by 472 · see citing works
Koelemeijer, R. B. A., Homan, C. D., & Matthijsen, J. (2006) · Atmospheric Environment · doi:10.1016/j.atmosenv.2006.04.044 · Cited by 401 · see citing works
Reduction of Particulate Air Pollution Lowers the Risk of Heritable Mutations in Mice
Somers, C. M., McCarry, B. E., Malek, F., & Quinn, J. S. (2004) · Science · doi:10.1126/science.1095815 · Cited by 318 · see citing works
Becker, S., Dailey, L. A., Soukup, J. M., Grambow, S. C., Devlin, R. B., & Huang, Y.-C. T. (2005) · Environmental Health Perspectives · doi:10.1289/ehp.7996 · Cited by 315 · see citing works
Hetland, R. B., Cassee, F. R., Refsnes, M., Schwarze, P. E., Låg, M., Boere, A. J. F., & Dybing, E. (2003) · Toxicology in Vitro · doi:10.1016/s0887-2333(03)00142-5 · Cited by 229 · see citing works
Gualtieri, M., Øvrevik, J., Holme, J. A., Perrone, M., Bolzacchini, E., Schwarze, P. E., & Camatini, M. (2009) · Toxicology in Vitro · doi:10.1016/j.tiv.2009.09.013 · Cited by 219 · see citing works
Self-citationBiomarkers of exposure to polycyclic aromatic hydrocarbons from environmental air pollution
Castaño‐Vinyals, G., d’Errico, A., Malats, N., & Kogevinas, M. (2004) · Occupational and Environmental Medicine · doi:10.1136/oem.2003.008375 · Cited by 198 · see citing works
Krewski, D. R., Burnett, R. T., Jerrett, M., Pope, C. A., Rainham, D. G. C., Calle, E. E., Thurston, G. D., & Thun, M. J. (2005) · Journal of Toxicology and Environmental Health · doi:10.1080/15287390590935941 · Cited by 196 · see citing works
Seasonal variations in chemical composition and in vitro biological effects of fine PM from Milan
Perrone, M., Gualtieri, M., Ferrero, L., et al. (2010) · Chemosphere · doi:10.1016/j.chemosphere.2009.12.071 · Cited by 193 · see citing works
Self-citationGremlin-mediated Decrease in Bone Morphogenetic Protein Signaling Promotes Pulmonary Fibrosis
Myllärniemi, M., Lindholm, P., Ryynänen, M. J., Kliment, C. R., Salmenkivi, K., Keski‐Oja, J., Kinnula, V. L., Oury, T. D., & Koli, K. M. (2007) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200706-945oc · Cited by 192 · see citing works
Levels of particulate matter in rural, urban and industrial sites in Spain
Querol, X., Alástuey, A., Rodrı́guez, S., et al. (2004) · The Science of The Total Environment · doi:10.1016/j.scitotenv.2004.04.036 · Cited by 177 · see citing works
Gualtieri, M., Øvrevik, J., Mollerup, S. K., Asare, N., Longhin, E., Dahlman, H. J., Camatini, M., & Holme, J. A. (2011) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2011.05.011 · Cited by 170 · see citing works
Self-citationBillet, S., Garçon, G., Dagher, Z., Verdin, A., Ledoux, F., Cazier, F., Courcot, D., Aboukaı̈s, A., & Shirali, P. (2007) · Environmental Research · doi:10.1016/j.envres.2007.03.001 · Cited by 170 · see citing works
Dagher, Z., Garçon, G., Billet, S., Gosset, P., Ledoux, F., Courcot, D., Aboukaı̈s, A., & Shirali, P. (2006) · Toxicology · doi:10.1016/j.tox.2006.04.038 · Cited by 168 · see citing works
KARLSSON, H., Ljungman, A. G., Lindbom, J., & MOLLER, L. (2006) · Toxicology Letters · doi:10.1016/j.toxlet.2006.04.003 · Cited by 166 · see citing works
Gualtieri, M., Mantecca, P., Corvaja, V., et al. (2009) · Toxicology Letters · doi:10.1016/j.toxlet.2009.03.003 · Cited by 148 · see citing works
Self-citationPavanello, S., Bollati, V., Pesatori, A. C., Kapka‐Skrzypczak, L., Bolognesi, C., Bertazzi, P. A., & Baccarelli, A. (2009) · International Journal of Cancer · doi:10.1002/ijc.24492 · Cited by 147 · see citing works
Polycyclic aromatic hydrocarbons induce both apoptotic and anti-apoptotic signals in Hepa1c1c7 cells
Solhaug, A. (2003) · Carcinogenesis · doi:10.1093/carcin/bgh069 · Cited by 135 · see citing works
Liu, H., Dong, H., Robertson, K. D., & Liu, C. (2011) · American Journal Of Pathology · doi:10.1016/j.ajpath.2010.10.023 · Cited by 128 · see citing works
Effect of chemical composition on the induction of DNA damage by urban airborne particulate matter
Gutiérrez-Castillo, M. E., Roubicek, D. A., Cebrián‐García, M. E., et al. (2005) · Environmental and Molecular Mutagenesis · doi:10.1002/em.20186 · Cited by 125 · see citing works
Primary and secondary carbonaceous species in PM2.5 samples in Milan (Italy)
Lonati, G., Ozgen, S., & Giugliano, M. (2007) · Atmospheric Environment · doi:10.1016/j.atmosenv.2007.03.046 · Cited by 125 · see citing works
Hockley, S. L., Arlt, V. M., Brewer, D. S., Giddings, I., & Phillips, D. H. (2006) · BMC Genomics · doi:10.1186/1471-2164-7-260 · Cited by 124 · see citing works
Diani-Moore, S., Ram, P., Li, X., Mondal, P., Youn, D. Y., Sauve, A. A., & Rifkind, A. B. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.131573 · Cited by 123 · see citing works
Ferecatu, I., Borot, M.-C., Bossard, C., Leroux, M., Boggetto, N., Marano, F., Baeza‐Squiban, A., & Andréau, K. (2010) · Particle and Fibre Toxicology · doi:10.1186/1743-8977-7-18 · Cited by 112 · see citing works
Farina, F., Sancini, G., Mantecca, P., Gallinotti, D., Camatini, M., & Palestini, P. (2011) · Toxicology Letters · doi:10.1016/j.toxlet.2011.01.031 · Cited by 110 · see citing works
Self-citationWong, L., Aung, H. H., Lamé, M. W., Wegesser, T. C., & Wilson, D. W. (2011) · Toxicology in Vitro · doi:10.1016/j.tiv.2011.06.001 · Cited by 104 · see citing works
Billet, S., Abbas, I., Goff, J. L., Verdin, A., André, V., Lafargue, P.-E., Hachimi, A., Cazier, F., Sichel, F., Shirali, P., et al. (2008) · Cancer Letters · doi:10.1016/j.canlet.2008.04.044 · Cited by 104 · see citing works
DNA damage response of A549 cells treated with particulate matter (PM 10 ) of urban air pollutants
Sánchez-Pérez, Y., Chirino, Y. I., Osornio-Vargas, Á. R., Morales‐Bárcenas, R., Gutiérrez‐Ruíz, M. C., Vázquez‐López, I., & García-Cuellar, C. M. (2009) · Cancer Letters · doi:10.1016/j.canlet.2009.01.010 · Cited by 100 · see citing works
Particulate matter inhibits DNA repair and enhances mutagenesis
Mehta, M., Chen, L., Gordon, T., Rom, W. N., & Tang, M. (2008) · Mutation Research/Genetic Toxicology and Environmental Mutagenesis · doi:10.1016/j.mrgentox.2008.08.015 · Cited by 99 · see citing works
AHR- and DNA-Damage-Mediated Gene Expression Responses Induced by Benzo(a)pyrene in Human Cell Lines
Hockley, S. L., Arlt, V. M., Brewer, D. S., Poele, R. T., Workman, P., Giddings, I., & Phillips, D. H. (2007) · Chemical Research in Toxicology · doi:10.1021/tx700252n · Cited by 98 · see citing works
Andrysík, Z., Vondráček, J., Marvanová, S., Cigánek, M., Neča, J., Pěnčíková, K., Mahadevan, B., Topinka, J., Baird, W. M., Kozubı́k, A., et al. (2011) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2011.06.011 · Cited by 94 · see citing works
Do Airborne Particles Induce Heritable Mutations?
Samet, J. M., DeMarini, D. M., & Malling, H. V. (2004) · Science · doi:10.1126/science.1097441 · Cited by 87 · see citing works
Bonetta, S., Gianotti, V., Bonetta, S., Gosetti, F., Oddone, M., Gennaro, M. C., & Carraro, E. (2009) · Chemosphere · doi:10.1016/j.chemosphere.2009.07.076 · Cited by 87 · see citing works
Induction of epithelial‐mesenchymal transition‐related genes by benzo[a]pyrene in lung cancer cells
Yoshino, I., Kometani, T., Shoji, F., Osoegawa, A., Ohba, T., Kouso, H., Takenaka, T., Yohena, T., & Maehara, Y. (2007) · Cancer · doi:10.1002/cncr.22728 · Cited by 85 · see citing works
Costello, C. M., Howell, K., Cahill, E., McBryan, J., Königshoff, M., Eickelberg, O., Gaine, S., Martin, F., & McLoughlin, P. (2008) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00358.2007 · Cited by 84 · see citing works
Genotoxicity of urban air pollutants in the Czech Republic
Topinka, J., Schwarz, L. R., Wiebel, F. J., et al. (2000) · Mutation Research/Genetic Toxicology and Environmental Mutagenesis · doi:10.1016/s1383-5718(00)00061-9 · Cited by 77 · see citing works
Binková, B., Veselý, D., Veselá, D., et al. (1999) · Mutation Research/Genetic Toxicology and Environmental Mutagenesis · doi:10.1016/s1383-5718(99)00011-x · Cited by 73 · see citing works
Kometani, T., Yoshino, I., Miura, N., Okazaki, H., Ohba, T., Takenaka, T., Shoji, F., Yano, T., & Maehara, Y. (2009) · Cancer Letters · doi:10.1016/j.canlet.2008.12.017 · Cited by 69 · see citing works
Transcriptional responses to complex mixtures—A review
Sen, B., Mahadevan, B., & DeMarini, D. M. (2007) · Mutation Research/Reviews in Mutation Research · doi:10.1016/j.mrrev.2007.08.002 · Cited by 69 · see citing works
Primary and secondary components of PM2.5 in Milan (Italy)
Lonati, G., Giugliano, M., & Ozgen, S. (2008) · Environment International · doi:10.1016/j.envint.2007.12.009 · Cited by 61 · see citing works
PM10‐biogenic fraction drives the seasonal variation of proinflammatory response in A549 cells
Camatini, M., Corvaja, V., Pezzolato, E., Mantecca, P., & Gualtieri, M. (2010) · Environmental Toxicology · doi:10.1002/tox.20611 · Cited by 60 · see citing works
Self-citationCastorena‐Torres, F., de León, M. B., Cisneros, B., Zapata‐Pérez, O., Salinas, J. E., & Albores, A. (2007) · Toxicology in Vitro · doi:10.1016/j.tiv.2007.10.009 · Cited by 59 · see citing works
Ma, Q. (2002) · Archives of Biochemistry and Biophysics · doi:10.1016/s0003-9861(02)00339-9 · Cited by 50 · see citing works
Sharma, A. K., Jensen, K. A., Rank, J., White, P. A., Lundstedt, S., Gagné, R., Jacobsen, N. R., Kristiansen, J., Vogel, U. B., & Wallin, H. (2007) · Mutation Research/Genetic Toxicology and Environmental Mutagenesis · doi:10.1016/j.mrgentox.2007.05.013 · Cited by 46 · see citing works
Wenger, D., Gerecke, A. C., Heeb, N. V., Hueglin, C., Seiler, C., Haag, R., Naegeli, H., & Zenobi, R. (2009) · Atmospheric Environment · doi:10.1016/j.atmosenv.2009.04.012 · Cited by 42 · see citing works
Mahadevan, B., Parsons, H., Musafia, T., et al. (2004) · Environmental and Molecular Mutagenesis · doi:10.1002/em.20039 · Cited by 34 · see citing works
Temporal variation in the genotoxic potential of urban air particulate matter
Sevastyanova, O., Nováková, Z. V., Hanzalová, K., et al. (2007) · Mutation Research/Genetic Toxicology and Environmental Mutagenesis · doi:10.1016/j.mrgentox.2007.09.010 · Cited by 30 · see citing works
Tian, L., Suzuki, M., Nakajima, T., et al. (2008) · Cancer · doi:10.1002/cncr.23694 · Cited by 27 · see citing works
(2002) · The Annals of Occupational Hygiene · doi:10.1093/annhyg/46.suppl_1.203 · Cited by 27 · see citing works
Arrieta, D. E., Ontiveros, C., Li, W.-W., et al. (2003) · Environmental Health Perspectives · doi:10.1289/ehp.6058 · Cited by 27 · see citing works
Assessment of dioxin-like activity in ambient air particulate matter using recombinant yeast assays
Olivares, A., van Drooge, B. L., Ballesta, P. P., Grimalt, J. O., & Piña, B. (2010) · Atmospheric Environment · doi:10.1016/j.atmosenv.2010.09.039 · Cited by 22 · see citing works
Application of Oligonucleotide Microarray Technology to Toxic Occupational Exposures
Gwinn, M. R., & Weston, A. (2008) · Journal of Toxicology and Environmental Health · doi:10.1080/15287390701738509 · Cited by 22 · see citing works
Nerriere, É., Zmirou‐Navier, D., Desqueyroux, P., et al. (2005) · Journal of Occupational and Environmental Medicine · doi:10.1097/01.jom.0000181757.82556.f7 · Cited by 15 · see citing works
ZERBI, G., FERRUGIARI, A., FUSTELLA, G., et al. (2008) · Virtual Community of Pathological Anatomy (University of Castilla La Mancha) · Cited by 5 · see citing works
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Deng, X., Zhang, F., Rui, W., Long, F., Wang, L., Feng, Z., Chen, D., & Ding, W. (2013) · Toxicology in Vitro · doi:10.1016/j.tiv.2013.05.004 · Cited by 400 · see citing works
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. (2018) · Archives of Toxicology · doi:10.1007/s00204-018-2197-9 · Cited by 339 · see citing works
- Authors
- Gualtieri, M., Longhin, E., Mattioli, M., Mantecca, P., Tinaglia, V., Mangano, E., Proverbio, M. C., Bestetti, G., Camatini, M., & Battaglia, C.
- Affiliations
- University of Milano-Bicocca (IT)
- University of Milan (IT)
- Institute of Biomedical Technologies (IT)
- Corresponding author
- Gualtieri, Maurizio
- ORCID
- Venue
- Toxicology Letters
- Publisher
- Elsevier BV
- Published
- 2012-03
- Volume
- 209
- Issue
- 2
- Pages
- 136-145
- ISSN
- 0378-4274 (ISSN-L)
- OpenAlex
- W2144112254
- Cited by
- 152
- References
- 61
- Citations by year
- 2026: 2 · 2025: 11 · 2024: 7 · 2023: 5 · 2022: 4 · 2021: 11 · 2020: 19 · 2019: 19 · 2018: 21 · 2017: 10 · 2016: 9 · 2015: 11 · 2014: 8 · 2013: 11 · 2012: 4
- FWCI
- 5.30
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Toxicology Letters (publishedVersion)
- PubMed (publishedVersion)
- BOA (University of Milano-Bicocca) (submittedVersion)
- Funders
- Università degli Studi di Milano
- Fondazione Cariplo
- Topics
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Air Quality and Health Impacts
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
- Keywords
- PM2.5, particulate matter, A549 cells, gene expression profiling, reactive oxygen species, DNA strand breaks, cytotoxicity, CYP1A1, CYP1B1, polycyclic aromatic hydrocarbons, oxidative stress, epiregulin, FOSL1, air pollution health effects
- MeSH terms
- Aryl Hydrocarbon Hydroxylases, Cell Line, Cell Survival, DNA Damage, Environmental Exposure, Epithelial Cells, Flow Cytometry, Humans, Italy, Polycyclic Aromatic Hydrocarbons, RNA, Seasons, Urban Population, Blotting, Western, Gene Expression, Reactive Oxygen Species, Reverse Transcriptase Polymerase Chain Reaction, Oligonucleotide Array Sequence Analysis, Comet Assay, Gene Expression Profiling, Particulate Matter, Real-Time Polymerase Chain Reaction, Cytochrome P-450 CYP1B1
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