Abstract
Human exposure to silica nanoparticles (SNPs) and formaldehyde (FA) is increasing and this has raised some concerns over their possible toxic effects on the exposed working populations. Notwithstanding several studies in this area, the combined toxicological effects of these contaminants have not been yet studied. Therefore, this in vitro study was designed to evaluate the SNPs and FA combined toxicity on human lung epithelial cells (A549 cells). The cells were exposed to SNPs and FA separately and in combined form and the single and combined toxicity of SNPs and FA were evaluated by focusing on cellular viability, DNA damage, and apoptosis via MTT, DAPI staining, DNA ladder, and Annexin V-FITC apoptosis assays. The results showed a significant increase in cytotoxicity, DNA damage, and chromatin fragmentation and late apoptotic\necrotic rates in combined treated cells compared with SNPs and FA-treated cells (P value < 0.05). Two-factorial analysis showed an additive toxic interaction between SNPs and FA. Eventually, this can be deduced that workers exposed simultaneously to SNPs and FA may be at high risk compared with exposure to each other.
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References
Ahamed M (2013) Silica nanoparticles-induced cytotoxicity, oxidative stress and apoptosis in cultured A431 and A549 cells. Hum Exp Toxicol 32:186–195
Andjelkovich DA, Janszen DB, Brown MH, Richardson RB, Miller FJ (1995) Mortality of iron foundry workers: IV. Analysis of a subcohort exposed to formaldehyde. J Occup Environ Med 37:826–837
Asweto C, Wu J, Hu H, Feng L, Yang X, Duan J, Sun Z (2017) Combined effect of silica nanoparticles and benzo [a] pyrene on cell cycle arrest induction and apoptosis in human umbilical vein endothelial cells. Int J Environ Res Public Health 14:289
Barillet S, Jugan M-L, Laye M, Leconte Y, Herlin-Boime N, Reynaud C, Carrière M (2010) In vitro evaluation of SiC nanoparticles impact on A549 pulmonary cells: cyto-, genotoxicity and oxidative stress. Toxicol Lett 198:324–330
Başaran N, Shubair M, Ündeğer Ü, Kars A (2003) Monitoring of DNA damage in foundry and pottery workers exposed to silica by the alkaline comet assay. Am J Ind Med 43:602–610
Bauer AT, Strozyk EA, Gorzelanny C, Westerhausen C, Desch A, Schneider MF, Schneider SW (2011) Cytotoxicity of silica nanoparticles through exocytosis of von Willebrand factor and necrotic cell death in primary human endothelial cells. Biomaterials 32:8385–8393
Berg JM, Romoser AA, Figueroa DE, West CS, Sayes CM (2013) Comparative cytological responses of lung epithelial and pleural mesothelial cells following in vitro exposure to nanoscale SiO 2. Toxicol in Vitro 27:24–33
Cancer IAfRo (2004) IARC classifies formaldehyde as carcinogenic to humans. Press release, 15
Cancer IAfRo (2005) Formaldehyde 2-butoxyethanol and 1-tertbutoxy-2-propanol in evaluating carcinogenic. Risk Hum 88:37–325
Chen M, von Mikecz A (2005) Formation of nucleoplasmic protein aggregates impairs nuclear function in response to SiO2 nanoparticles. Exp Cell Res 305:51–62
Cheng Y-H, Chao Y-C, Wu C-H, Tsai C-J, Uang S-N, Shih T-S (2008) Measurements of ultrafine particle concentrations and size distribution in an iron foundry. J Hazard Mater 158:124–130
Conde J, Doria G, Baptista P (2012) Noble metal nanoparticles applications in cancer. J Drug Deliv. https://doi.org/10.1155/2012/751075
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 2:10
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
Eskandani M, Hamishehkar H, Dolatabadi JEN (2013) Cyto/genotoxicity study of polyoxyethylene (20) sorbitan monolaurate (tween 20). DNA Cell Biol 32:498–503
Eskandani M, Hamishehkar H, Ezzati Nazhad Dolatabadi J (2014) Cytotoxicity and DNA damage properties of tert-butylhydroquinone (TBHQ) food additive. Food Chem 153:315–320
Evans DE, Heitbrink WA, Slavin TJ, Peters TM (2007) Ultrafine and respirable particles in an automotive grey iron foundry. Ann Occup Hyg 52:9–21
Ezzati Nazhad Dolatabadi J, Azami A, Mohammadi A, Hamishehkar H, Panahi-Azar V, Rahbar Saadat Y, Saei AA (2018) Formulation, characterization and cytotoxicity evaluation of ketotifen-loaded nanostructured lipid carriers. J Drug Deliv Sci Technol 46:268–273
Gangwal S, Brown JS, Wang A, Houck KA, Dix DJ, Kavlock RJ, Hubal EAC (2011) Informing selection of nanomaterial concentrations for ToxCast in vitro testing based on occupational exposure potential. Environ Health Perspect 119:1539–1546
Hamishehkar H, Khani S, Kashanian S, Ezzati Nazhad Dolatabadi J, Eskandani M (2014) Geno- and cytotoxicity of propyl gallate food additive. Drug Chem Toxicol 37:241–246
Kreyling WG, Semmler-Behnke M, Chaudhry Q (2010) A complementary definition of nanomaterial. Nano Today 5:165–168
Kum C, Kiral F, Sekkin S, Seyrek K, Boyacioglu M (2007) Effects of xylene and formaldehyde inhalations on oxidative stress in adult and developing rats livers. Exp Anim 56:35–42
Kum S, Sandikci M, Eren U, Metin N (2010) Effects of formaldehyde and xylene inhalations on fatty liver and kidney in adult and developing rats. J Anim Vet Adv 9:396–401
Lim SK, Kim JC, Moon CJ, Kim GY, Han HJ, Park SH (2010) Formaldehyde induces apoptosis through decreased Prx 2 via p38 MAPK in lung epithelial cells. Toxicology 271:100–106
Lu C-F, Yuan X-Y, Li L-Z, Zhou W, Zhao J, Wang Y-M, Peng S-Q (2015) Combined exposure to nano-silica and lead induced potentiation of oxidative stress and DNA damage in human lung epithelial cells. Ecotoxicol Environ Saf 122:537–544
Lu C-F, Li L-Z, Zhou W, Zhao J, Wang Y-M, Peng S-Q (2017) Silica nanoparticles and lead acetate co-exposure triggered synergistic cytotoxicity in A549 cells through potentiation of mitochondria-dependent apoptosis induction. Environ Toxicol Pharmacol 52:114–120
Matalová E, Španová A (2002) Detection of apoptotic DNA ladder in pig leukocytes and its precision using LM-PCR (ligation mediated polymerase chain reaction). Acta Vet Brno 71:163–168
Maynard AD, Aitken RJ, Butz T, Colvin V, Donaldson K, Oberdörster G, Philbert MA, Ryan J, Seaton A, Stone V (2006) Safe handling of nanotechnology. Nature 444:267
Mizuki M, Tsuda T (2001) Relationship between atopic factors and physical symptoms induced by gaseous formaldehyde exposure during an anatomy dissection course. Arerugi 50:21–28
Mohammadzadeh-Aghdash H, Sohrabi Y, Mohammadi A, Shanehbandi D, Dehghan P, Ezzati Nazhad Dolatabadi J (2018) Safety assessment of sodium acetate, sodium diacetate and potassium sorbate food additives. Food Chem 257:211–215
Nabeshi H, Yoshikawa T, Matsuyama K, Nakazato Y, Matsuo K, Arimori A, Isobe M, Tochigi S, Kondoh S, Hirai T (2011) Systemic distribution, nuclear entry and cytotoxicity of amorphous nanosilica following topical application. Biomaterials 32:2713–2724
Napierska D, Thomassen LC, Lison D, Martens JA, Hoet PH (2010) The nanosilica hazard: another variable entity. Part Fibre Toxicol 7:39
Neuss S, Speit G (2008) Further characterization of the genotoxicity of formaldehyde in vitro by the sister chromatid exchange test and co-cultivation experiments. Mutagenesis 23:355–357
Oberdorster G, Oberdorster E, Oberdorster J (2005) Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles. Environ Health Perspect 113:823–839
Oberdörster G, Maynard A, Donaldson K, Castranova V, Fitzpatrick J, Ausman K, Carter J, Karn B, Kreyling W, Lai D (2005a) Principles for characterizing the potential human health effects from exposure to nanomaterials: elements of a screening strategy. Part Fibre Toxicol 2:8
Oberdörster G, Oberdörster E, Oberdörster J (2005b) Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles. Environ Health Perspect 113:823
Oudiz J, Brown JW, Ayer HE, Samuels S (1983) A report on silica exposure levels in United States foundries. Am Ind Hyg Assoc J 44:374–376
Park E-J, Park K (2009) Oxidative stress and pro-inflammatory responses induced by silica nanoparticles in vivo and in vitro. Toxicol Lett 184:18–25
Pelucchi C, Pira E, Piolatto G, Coggiola M, Carta P, La Vecchia C (2006) Occupational silica exposure and lung cancer risk: a review of epidemiological studies 1996–2005. Ann Oncol 17:1039–1050
Petushok N (2000) Activity of glutathione-related enzymes in rat tissues after formaldehyde exposure. Curr Top Biophys 24:167–170
Powers KW, Brown SC, Krishna VB, Wasdo SC, Moudgil BM, Roberts SM (2006) Research strategies for safety evaluation of nanomaterials. Part VI. Characterization of nanoscale particles for toxicological evaluation. Toxicol Sci 90:296–303
Rezazadeh MA, Mohammadian Y, Pourahmad J, Khodagholi F, Peirovi H, Mehrabi Y, Omidi M, Rafieepour A (2019) Individual and combined toxicity of carboxylic acid functionalized multi-walled carbon nanotubes and benzo a pyrene in lung adenocarcinoma cells. Environ Sci Pollut Res Int 26(13):12709–12719
Saadat YR, Saeidi N, Vahed SZ, Barzegari A, Barar J (2015) An update to DNA ladder assay for apoptosis detection. Bioimpacts 5:25
Sanchez-Perez Y, Chirino YI, Osornio-Vargas AR, Morales-Barcenas R, Gutierrez-Ruiz C, Vazquez-Lopez I, Garcia-Cuellar CM (2009) DNA damage response of A549 cells treated with particulate matter (PM10) of urban air pollutants. Cancer Lett 278:192–200
Sayes CM, Marchione AA, Reed KL, Warheit DB (2007) Comparative pulmonary toxicity assessments of C60 water suspensions in rats: few differences in fullerene toxicity in vivo in contrast to in vitro profiles. Nano Lett 7:2399–2406
Schmid O, Speit G (2007) Genotoxic effects induced by formaldehyde in human blood and implications for the interpretation of biomonitoring studies. Mutagenesis 22:69–74
Shaham J, Bomstein Y, Meltzer A, Kaufman Z, Palma E, Ribak J (1996) DNA-protein crosslinks, a biomarker of exposure to formaldehyde—in vitro and in vivo studies. Carcinogenesis 17:121–126
Sögüt S, Songur A, Özen OA, Özyurt H, Sarsilmaz M (2004) Does the subacute (4-week) exposure to formaldehyde inhalation lead to oxidant/antioxidant imbalance in rat liver. Eur J Gen Med 29:406–409
Sohrabi Y, Mohammadzadeh-Aghdash H, Baghbani E, Dehghan P, Ezzati Nazhad Dolatabadi J (2018) Cytotoxicity and genotoxicity assessment of ascorbyl palmitate (AP) food additive. Adv Pharm Bull 8:341–346
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
Tong R, Cheng M, Ma X, Yang Y, Liu Y, Li J (2019) Quantitative health risk assessment of inhalation exposure to automobile foundry dust. Environ Geochem Health 41(5):2179–2193
Wang F, Jiao C, Liu J, Yuan H, Lan M, Gao F (2011) Oxidative mechanisms contribute to nanosize silican dioxide-induced developmental neurotoxicity in PC12 cells. Toxicol in Vitro 25:1548–1556
Westberg H, Loefstedt H, Selden A, Lilja B-G, Naystroem P (2005) Exposure to low molecular weight isocyanates and formaldehyde in foundries using hot box core binders. Ann Occup Hyg 49:719–725
Wu J, Shi Y, Asweto CO, Feng L, Yang X, Zhang Y, Hu H, Duan J, Sun Z (2016) 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
Xie G, Sun J, Zhong G, Shi L, Zhang D (2010) Biodistribution and toxicity of intravenously administered silica nanoparticles in mice. Arch Toxicol 84:183–190
Xu Z, Chou L, Sun J (2012) Effects of SiO2 nanoparticles on HFL-I activating ROS-mediated apoptosis via p53 pathway. J Appl Toxicol 32:358–364
Yang X, Liu J, He H, Zhou L, Gong C, Wang X, Yang L, Yuan J, Huang H, He L (2010) SiO 2 nanoparticles induce cytotoxicity and protein expression alteration in HaCaT cells. Part Fibre Toxicol 7:1
Yang YX, Song ZM, Cheng B, Xiang K, Chen XX, Liu JH, Cao A, Wang Y, Liu Y, Wang H (2014) Evaluation of the toxicity of food additive silica nanoparticles on gastrointestinal cells. J Appl Toxicol 34:424–435
Yang X, Feng L, Zhang Y, Hu H, Shi Y, Liang S, Zhao T, Cao L, Duan J, Sun Z (2018) Co-exposure of silica nanoparticles and methylmercury induced cardiac toxicity in vitro and in vivo. Sci Total Environ 631:811–821
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
Zararsiz I, Sonmez MF, Yilmaz HR, Tas U, Kus I, Kavakli A, Sarsilmaz M (2006) Effects of v-3 essential fatty acids against formaldehyde-induced nephropathy in rats. Toxicol Ind Health 22:223–229
Zhang L, Tang X, Rothman N, Vermeulen R, Ji Z, Shen M, Qiu C, Guo W, Liu S, Reiss B (2010a) Occupational exposure to formaldehyde, hematotoxicity, and leukemia-specific chromosome changes in cultured myeloid progenitor cells. Cancer Epidemiol Biomarkers Prev 19:80–88
Zhang M, Zheng Y-D, Xie-Yi D, Yang L, Wen-Jie L, Cheng Q, Zheng-Lai W (2010b) Silicosis in automobile foundry workers: a 29-year cohort study. Biomed Environ Sci 23:121–129
Zhou DX, Qiu SD, Zhang J, Tian H, Wang HX (2006) The protective effect of vitamin E against oxidative damage caused by formaldehyde in the testes of adult rats. Asian J Androl 8:584–588
Zhu J, Liao L, Zhu L, Zhang P, Guo K, Kong J, Ji C, Liu B (2013) Size-dependent cellular uptake efficiency, mechanism, and cytotoxicity of silica nanoparticles toward HeLa cells. Talanta 107:408–415
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The authors are grateful for the financial support of this study by the Tabriz University of Medical Sciences, which was a part of M.Sc thesis No: B/368, Tabriz, Iran.
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Statement of novelty
Workers are exposed simultaneously with silica nanoparticles (SNPs) and formaldehyde (FA) in some industrial settings such as foundry factories. For the first time, the present research was designed to evaluate combined toxicity of SNPs and FA on A549 cell line by focusing on cellular viability, DNA damage, and apoptosis via MTT, DAPI staining, DNA ladder, and Annexin V-FITC apoptosis assays.
This study leaded to useful information on the formulation or revision of permissible occupational exposure limits and accurate risk assessment for all people exposed to SNPs and FA. However, further studies are needed.
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Highlights
• Single and combined toxicity of SNPs and FA were evaluated.
• SNPs and FA co-exposure caused DNA damage and apoptosis in A549 cells.
• The results showed an additive toxic interaction between SNPs and FA.
• Workers exposed simultaneously to SNPs and FA may be at high risk.
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Nazarparvar-Noshadi, M., Ezzati Nazhad Dolatabadi, J., Rasoulzadeh, Y. et al. Apoptosis and DNA damage induced by silica nanoparticles and formaldehyde in human lung epithelial cells. Environ Sci Pollut Res 27, 18592–18601 (2020). https://doi.org/10.1007/s11356-020-08191-8
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DOI: https://doi.org/10.1007/s11356-020-08191-8