Abstract
Both ultrafine particles (UFP) and polycyclic aromatic hydrocarbons (PAHs) are widely present in the environment, thus increasing their chances of exposure to human in the daily life. However, the study on the combined toxicity of UFP and PAHs on respiratory system is still limited. In this study, we examined the potential interactive effects of silica nanoparticles (SiNPs) and benzo[a]pyrene (B[a]P) in bronchial epithelial cells (BEAS-2B). Cells were exposed to SiNPs and B[a]P alone or in combination for 24 h. Co-exposure to SiNPs and B[a]P enhanced the malondialdehyde (MDA) contents and reduced superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities significantly, while the reactive oxygen species (ROS) generation had a slight increase in the exposed groups compared to the control but not statistically significant. Cell cycle arrest induced by the co-exposure showed a significant percentage increase in G2/M phase cells and a decrease in G0/G1 phase cells. In addition, there was a significant increase in BEAS-2B cells multinucleation as well as DNA damage. Cellular apoptosis was markedly increased even at the low-level co-exposure. Our results suggest that co-exposure to SiNPs and B[a]P exerts synergistic and additive cytotoxic and genotoxic effects.
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Albanese A, Tang PS, Chan WC (2012) The effect of nanoparticle size, shape, and surface chemistry on biological systems. Annu Rev Biomed Eng 14:1–16
Alinovi R, Goldoni M, Pinelli S, Campanini M, Aliatis I, Bersani D, Lottici PP, Iavicoli S, Petyx M, Mozzoni P (2015) Oxidative and pro-inflammatory effects of cobalt and titanium oxide nanoparticles on aortic and venous endothelial cells. Toxicol in Vitro 29:426–437
Argyo C, Weiss V, Bräuchle C, Bein T (2013) Multifunctional mesoporous silica nanoparticles as a universal platform for drug delivery. Chem Mater 26:435–451
Arlt VM, Krais AM, Godschalk RW, Riffo-Vasquez Y, Mrizova I, Roufosse CA, Corbin C, Shi Q, Frei E, Stiborova M (2015) Pulmonary inflammation impacts on CYP1A1-mediated respiratory tract DNA damage induced by the carcinogenic air pollutant benzo [a] pyrene. Toxicol Sci 146:213–225
Atkinson RW, Fuller GW, Anderson HR, Harrison RM, Armstrong B (2010) Urban ambient particle metrics and health: a time-series analysis. Epidemiology 21:501–511
Ba Q, Li J, Huang C, Qiu H, Li J, Chu R, Zhang W, Xie D, Wu Y, Wang H (2015) Effects of benzo [a] pyrene exposure on human hepatocellular carcinoma cell angiogenesis, metastasis, and NF-κB signaling. Environ Health Perspect 123:246
Balsara BR, Testa JR (2002) Chromosomal imbalances in human lung cancer. Oncogene 21:6877–6883
Breitner S, Liu L, Cyrys J, Brüske I, Franck U, Schlink U, Leitte AM, Herbarth O, Wiedensohler A, Wehner B (2011) Sub-micrometer particulate air pollution and cardiovascular mortality in Beijing, China. Sci Total Environ 409:5196–5204
Brown JS, Gordon T, Price O, Asgharian B (2013) Thoracic and respirable particle definitions for human health risk assessment. Part Fibre Toxicol 10:1
Bruce V (2015) Effects of low-dose gamma radiation in a murine model of benzo [a] pyrene-induced lung cancer.
Cai X, Hu X, Tan X, Cheng W, Wang Q, Chen X, Guan Y, Chen C, Jing X (2015) Metformin induced AMPK activation, G0/G1 phase cell cycle arrest and the inhibition of growth of esophageal squamous cell carcinomas in vitro and in vivo. PLoS One 10:e0133349
Chaudhry Q, Castle L (2011) Food applications of nanotechnologies: an overview of opportunities and challenges for developing countries. Trends Food Sci Technol 22:595–603
Chen Y, Huang C, Bai C, Gao H, Ma R, Liu X, Dong Q (2013) Benzo [α] pyrene repressed DNA mismatch repair in human breast cancer cells. Toxicology 304:167–172
Cocco P, Rice CH, Chen JQ, McCawley MA, McLaughlin JK, Dosemeci M (2001) Lung cancer risk, silica exposure, and silicosis in Chinese mines and pottery factories: the modifying role of other workplace lung carcinogens. Am J Ind Med 40:674–682
Donaldson K, Tran L, Jimenez LA, Duffin R, Newby DE, Mills N, MacNee W, Stone V (2005) Combustion-derived nanoparticles: a review of their toxicology following inhalation exposure. Part Fibre Toxicol 2:1
Downward GS, Hu W, Large D, Veld H, Xu J, Reiss B, Wu G, Wei F, Chapman RS, Rothman N (2014) Heterogeneity in coal composition and implications for lung cancer risk in Xuanwei and Fuyuan counties, China. Environ Int 68:94–104
Duan J, Hu H, Li Q, Jiang L, Zou Y, Wang Y, Sun Z (2016a) Combined toxicity of silica nanoparticles and methylmercury on cardiovascular system in zebrafish (Danio rerio) embryos. Environ Toxicol Pharmacol 44:120–127
Duan J, Yu Y, Li Y, Wang Y, Sun Z (2016b) Inflammatory response and blood hypercoagulable state induced by low level co-exposure with silica nanoparticles and benzo [a] pyrene in zebrafish (Danio rerio) embryos. Chemosphere 151:152–162
Duan J, Yu Y, Li Y, Yu Y, Li Y, Zhou X, Huang P, Sun Z (2013) Toxic effect of silica nanoparticles on endothelial cells through DNA damage response via Chk1-dependent G2/M checkpoint. PLoS One 8:e62087
Duan J, Yu Y, Yu Y, Li Y, Huang P, Zhou X, Peng S, Sun Z (2014) Silica nanoparticles enhance autophagic activity, disturb endothelial cell homeostasis and impair angiogenesis. Part Fibre Toxicol 11:1–13
EPA (2002) Health assessment document for diesel engine exhaust. National Center for Environmental Assessment
Franck U, Odeh S, Wiedensohler A, Wehner B, Herbarth O (2011) The effect of particle size on cardiovascular disorders—the smaller the worse. Sci Total Environ 409:4217–4221
Gilli G, Pignata C, Schilirò T, Bono R, La Rosa A, Traversi D (2007) The mutagenic hazards of environmental PM2.5 in Turin. Environ Res 103:168–175
Hamouchene H, Arlt VM, Giddings I, Phillips DH (2011) Influence of cell cycle on responses of MCF-7 cells to benzo [a] pyrene. BMC Genomics 12:1
He X, Asthana S, Sorger PK (2000) Transient sister chromatid separation and elastic deformation of chromosomes during mitosis in budding yeast. Cell 101:763–775
Huang Y, Fulton AN, Keller AA (2016) Optimization of porous structure of superparamagnetic nanoparticle adsorbents for higher and faster removal of emerging organic contaminants and PAHs. Environ Sci Water Res Technol 2:521–528
IARC (2010) Some non-heterocyclic polycyclic aromatic hydrocarbons and some related exposures. IARC Monog Eval Carcinog Risks Humans/World Health Org, Int Agency Res Cancer 92:1
Jomova K, Valko M (2011) Advances in metal-induced oxidative stress and human disease. Toxicology 283:65–87
Jones RG, Plas DR, Kubek S, Buzzai M, Mu J, Xu Y, Birnbaum MJ, Thompson CB (2005) AMP-activated protein kinase induces a p53-dependent metabolic checkpoint. Mol Cell 18:283–293
Kang J-H, Keller JJ, Chen C-S, Lin H-C (2012) Asian dust storm events are associated with an acute increase in pneumonia hospitalization. Ann Epidemiol 22:257–263
Kelly FJ, Fussell JC (2012) Size, source and chemical composition as determinants of toxicity attributable to ambient particulate matter. Atmos Environ 60:504–526
Khatri M, Bello D, Gaines P, Martin J, Pal AK, Gore R, Woskie S (2013) Nanoparticles from photocopiers induce oxidative stress and upper respiratory tract inflammation in healthy volunteers. Nanotoxicology 7:1014–1027
Kumar P, Robins A, Vardoulakis S, Britter R (2010) A review of the characteristics of nanoparticles in the urban atmosphere and the prospects for developing regulatory controls. Atmos Environ 44:5035–5052
Large DJ, Kelly S, Spiro B, Tian L, Shao L, Finkelman R, Zhang M, Somerfield C, Plint S, Ali Y (2009) Silica–volatile interaction and the geological cause of the Xuan Wei lung cancer epidemic. Environ Sci Technol 43:9016–9021
Leverson JD, H-k H, Forsburg SL, Hunter T (2002) The Schizosaccharomyces pombe aurora–related kinase Ark1 interacts with the inner centromere protein Pic1 and mediates chromosome segregation and cytokinesis. Mol Biol Cell 13:1132–1143
Li Q, Hu H, Jiang L, Zou Y, Duan J, SUN Z (2016): Cytotoxicity and autophagy dysfunction induced by different size of silica particles in human bronchial epithelial BEAS-2B cells. Toxicol Res
Li Y, Zhu T, Zhao J, Xu B (2012) Interactive enhancements of ascorbic acid and iron in hydroxyl radical generation in quinone redox cycling. Environ Sci Technol 46:10302–10309
Lim H, Bergvall C, Jarvis I, Mattsson Å, Dreij K, Stenius U, Westerholm R (2014) Benzo [a] pyrene-specific online high-performance liquid chromatography fractionation of air particulate extracts–a tool for evaluating biological interactions. J Chromatogr A 1355:100–106
Lin H, Ning B, Li J, Ho SC, Huss A, Vermeulen R, Tian L (2015) Lung Cancer Mortality Among Women in Xuan Wei, China: A Comparison of Spatial Clustering Detection Methods. Asia Pac J Public Health 27(2):392–401
Lindeman TE, Poirier MC, Divi RL (2011) The resveratrol analogue, 2, 3′, 4, 5′-tetramethoxystilbene, does not inhibit CYP gene expression, enzyme activity and benzo [a] pyrene–DNA adduct formation in MCF-7 cells exposed to benzo [a] pyrene. Mutagenesis 26:629–635
Madl AK, Pinkerton KE (2009) Health effects of inhaled engineered and incidental nanoparticles. Crit Rev Toxicol 39:629–658
Matassoni L, Pratesi G, Centioli D, Cadoni F, Lucarelli F, Nava S, Malesani P (2011) Saharan dust contribution to PM 10, PM 2.5 and PM 1 in urban and suburban areas of Rome: a comparison between single-particle SEM-EDS analysis and whole-sample PIXE analysis. J Environ Monit 13:732–742
McClean M, Rinehart R, Ngo L, Eisen E, Kelsey K, Wiencke J, Herrick R (2004) Urinary 1-hydroxypyrene and polycyclic aromatic hydrocarbon exposure among asphalt paving workers. Ann Occup Hyg 48:565–578
Melchini A, Catania S, Stancanelli R, Tommasini S, Costa C (2011) Interaction of a functionalized complex of the flavonoid hesperetin with the AhR pathway and CYP1A1 expression: involvement in its protective effects against benzo [a] pyrene-induced oxidative stress in human skin. Cell Biol Toxicol 27:371–379
Mendoza A, Torres-Hernandez JA, Ault JG, Pedersen-Lane JH, Gao D, Lawrence DA (2014) Silica nanoparticles induce oxidative stress and inflammation of human peripheral blood mononuclear cells. Cell Stress Chaperones 19:777–790
Møller P, Danielsen PH, Karottki DG, Jantzen K, Roursgaard M, Klingberg H, Jensen DM, Christophersen DV, Hemmingsen JG, Cao Y (2014) Oxidative stress and inflammation generated DNA damage by exposure to air pollution particles. Mutat Res/Rev Mutat Res 762:133–166
Nabeshi H, Yoshikawa T, Matsuyama K, Nakazato Y, Tochigi S, Kondoh S, Hirai T, Akase T, Nagano K, Abe Y (2011) Amorphous nanosilica induce endocytosis-dependent ROS generation and DNA damage in human keratinocytes. Part Fibre Toxicol 8:1
Napierska D, Thomassen LC, Lison D, Martens JA, Hoet PH (2010) The nanosilica hazard: another variable entity. Part Fibre Toxicol 7:1
Nemmar A, Albarwani S, Beegam S, Yuvaraju P, Yasin J, Attoub S, Ali BH (2014) Amorphous silica nanoparticles impair vascular homeostasis and induce systemic inflammation. Int J Nanomedicine 9:2779
Nemmar A, Holme JA, Rosas I, Schwarze PE, Alfaro-Moreno E (2013): Recent advances in particulate matter and nanoparticle toxicology: a review of the in vivo and in vitro studies. BioMed Res Int 2013
Nemmar A, Yuvaraju P, Beegam S, Yasin J, Kazzam EE, Ali BH (2016) Oxidative stress, inflammation, and DNA damage in multiple organs of mice acutely exposed to amorphous silica nanoparticles. Int J Nanomedicine 11:919
Ouyang L, Shi Z, Zhao S, Wang FT, Zhou TT, Liu B, Bao JK (2012) Programmed cell death pathways in cancer: a review of apoptosis, autophagy and programmed necrosis. Cell Prolif 45:487–498
Pailler E, Auger N, Lindsay C, Vielh P, Islas-Morris-Hernandez A, Borget I, Ngo-Camus M, Planchard D, Soria J-C, Besse B (2015): High level of chromosomal instability in circulating tumor cells of ROS1-rearranged non-small-cell lung cancer. Ann Oncol, mdv165
Pink M, Verma N, Rettenmeier AW, Schmitz-Spanke S (2014) Integrated proteomic and metabolomic analysis to assess the effects of pure and benzo [a] pyrene-loaded carbon black particles on energy metabolism and motility in the human endothelial cell line EA. hy926. Arch Toxicol 88:913–934
Puente BN, Kimura W, Muralidhar SA, Moon J, Amatruda JF, Phelps KL, Grinsfelder D, Rothermel BA, Chen R, Garcia JA (2014) The oxygen-rich postnatal environment induces cardiomyocyte cell-cycle arrest through DNA damage response. Cell 157:565–579
Rieder CL (2011) Mitosis in vertebrates: the G2/M and M/a transitions and their associated checkpoints. Chromosom Res 19:291–306
Shi P, Chandra J, Sun X, Gergely M, Cortes JE, Garcia-Manero G, Arlinghaus RB, Lai R, Amin HM (2010) Inhibition of IGF-IR tyrosine kinase induces apoptosis and cell cycle arrest in imatinib-resistant chronic myeloid leukaemia cells. J Cell Mol Med 14:1777–1792
Škarek M, Janošek J, Čupr P, Kohoutek J, Novotna-Rychetska A, Holoubek I (2007) Evaluation of genotoxic and non-genotoxic effects of organic air pollution using in vitro bioassays. Environ Int 33:859–866
Sun L, Li Y, Liu X, Jin M, Zhang L, Du Z, Guo C, Huang P, Sun Z (2011) Cytotoxicity and mitochondrial damage caused by silica nanoparticles. Toxicol in Vitro 25:1619–1629
Tian L, Dai S, Wang J, Huang Y, Ho SC, Zhou Y, Lucas D, Koshland CP (2008) Nanoquartz in late Permian C1 coal and the high incidence of female lung cancer in the Pearl River origin area: a retrospective cohort study. BMC Public Health 8:1
Vakharia DD, Liu N, Pause R, Fasco M, Bessette E, Zhang Q-Y, Kaminsky LS (2001) Polycyclic aromatic hydrocarbon/metal mixtures: effect on PAH induction of CYP1A1 in human HEPG2 cells. Drug Metab Dispos 29:999–1006
Wang W, Li Y, Liu X, Jin M, Du H, Liu Y, Huang P, Zhou X, Yuan L, Sun Z (2013) Multinucleation and cell dysfunction induced by amorphous silica nanoparticles in an L-02 human hepatic cell line. Int J Nanomedicine 8:3533
Wannhoff A, Bölck B, Kübler A, Bloch W, Reuther T (2013) Oxidative and nitrosative stress and apoptosis in oral mucosa cells after ex vivo exposure to lead and benzo [a] pyrene. Toxicol in Vitro 27:915–921
WHO (2013) Health effects of particulate matter. Policy implications for countries in eastern Europe, Caucasus and Central Asia. World Health Organization Regional Office for Europe, Copenhagen
Yu Y, Duan J, Li Y, Yu Y, Jin M, Li C, Wang Y, Sun Z (2015) Combined toxicity of amorphous silica nanoparticles and methylmercury to human lung epithelial cells. Ecotoxicol Environ Saf 112:144–152
Zhu W, Cromie MM, Cai Q, Lv T, Singh K, Gao W (2014) Curcumin and vitamin E protect against adverse effects of benzo [a] pyrene in lung epithelial cells. PLoS One 9:e92992
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This work was supported by the National Natural Science Foundation of China (Nos. 81230065 and 81571130090) and Special Project of Beijing Municipal Science & Technology Commission (KZ201410025022).
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Wu, J., Shi, Y., Asweto, C.O. et al. Co-exposure to amorphous silica nanoparticles and benzo[a]pyrene at low level in human bronchial epithelial BEAS-2B cells. Environ Sci Pollut Res 23, 23134–23144 (2016). https://doi.org/10.1007/s11356-016-7559-3
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DOI: https://doi.org/10.1007/s11356-016-7559-3