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In vitro genotoxicity of asbestos substitutes induced by coupled stimulation of dissolved high-valence ions and oxide radicals

  • Interface Effect of Ultrafine Mineral Particles and Microorganisms
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Abstract

The wide use of asbestos and its substitutes has given rise to studies on their possible harmful effects on human health and environment. However, their toxic effects remain unclear. The present study was aimed to disclose the coupled effects of dissolved high-valence ions and oxide radicals using the in vitro cytotoxicity and genotoxicity of chrysotile (CA), nano-SiO2 (NS), ceramic fiber (CF), glass fiber (GF), and rock wool (RW) on Chinese hamster lung cells V79. All samples induced cell mortality correlated well with the chemical SiO2 content of asbestos substitutes and the amount of dissolved Si. Alkali or alkaline earth metal elements relieved mortality of V79 cells; Al2O3 reinforced toxicity of materials. Asbestos substitutes generated lasting, increasing amount of acellular ·OH which formed at the fiber surface at sites with loose/unsaturated bonds, as well as by catalytic reaction through dissolved iron. Accumulated mechanical and radical stimulation induced the intracellular reactive oxygen species (ROS) elevation, morphology change, and deviating trans-membrane ion flux. The cellular ROS appeared as NS > GF > CF ≈ CA > RW, consistent with cell mortality rather than with acellular ·OH generation. Chromosomal and DNA lesions in V79 cells were not directly associated with the cellular ROS, while influenced by dissolved high-valence irons in the co-culture medium. In conclusion, ions from short-time dissolution of dust samples and the generation of extracellular ·OH presented combined effects in the elevation of intracellular ROS, which further synergistically induced cytotoxicity and genotoxicity.

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References

  • Anonymous (1986) Environmental health criteria 53: asbestos and other natural mineral fibers, international programme on chemical safety. World Health Organization, Geneva

    Google Scholar 

  • Anonymous (2002) Man-made vitreous fibres, IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. World Health Organization International Agency for Research on Cancer

    Google Scholar 

  • Armand L, Tarantini A, Beal D, Biola-Clier M, Bobyk L, Sorieul S, Pernet-Gallay K, Marie-Desvergne C, Lynch I, Herlin-Boime N (2016) Long-term exposure of A549 cells to titanium dioxide nanoparticles induces DNA damage and sensitizes cells towards genotoxic agents. Nanotoxicology 10:913–923

    Article  CAS  Google Scholar 

  • Aust AE, Cook PM, Dodson RF (2011) Morphological and chemical mechanisms of elongated mineral particle toxicities. J Toxicol Environ Health, Pt. B Crit Rev 14:40–75

    Article  CAS  Google Scholar 

  • Baur X, Soskolne CL, Lemen RA, Schneider J, Woitowitz H-J, Budnik LT (2015) How conflicted authors undermine the World Health Organization (WHO) campaign to stop all use of asbestos: spotlight on studies showing that chrysotile is carcinogenic and facilitates other non-cancer asbestos-related diseases. Int J Occup Environ Health 21:176–179

    Article  CAS  Google Scholar 

  • Benjamin H, Lebanony D, Rosenwald S, Cohen L, Gibori H, Barabash N, Ashkenazi K, Goren E, Meiri E, Morgenstern S (2010) A diagnostic assay based on microRNA expression accurately identifies malignant pleural mesothelioma. J Mol Diagn 12:771–779

    Article  CAS  Google Scholar 

  • Berlo DV, Clift MJ, Albrecht C, Schins RP (2012) Carbon nanotubes: an insight into the mechanisms of their potential genotoxicity. Swiss Med Wkly 142:w13698

    Google Scholar 

  • Bernareggi A, Ren E, Borelli V, Vita F, Constanti A, Zabucchi G (2015): Xenopus laevis oocytes as a model system for studying the interaction between asbestos fibres and cell membranes. Toxicol. Sci., kfv050

  • Bernstein D, Dunnigan J, Hesterberg T, Brown R, Velasco JAL, Barrera R, Hoskins J, Gibbs A (2013) Health risk of chrysotile revisited. Crit Rev Toxicol 43:154–183

    Article  CAS  Google Scholar 

  • Bernstein DM, Riego Sintes JM, Bjarne KE, Kunert J (2001) Biopersistence of synthetic mineral fibers as a predictor of chronic inhalation toxicity in rats. Inhal Toxicol 13:823–849

    Article  CAS  Google Scholar 

  • Bernstein DM, Rogers RA, Sepulveda R, Kunzendorf P, Bellmann B, Ernst H, Creutzenberg O, Phillips JI (2015) Evaluation of the fate and pathological response in the lung and pleura of brake dust alone and in combination with added chrysotile compared to crocidolite asbestos following short-term inhalation exposure. Toxicol Appl Pharmacol 283:20–34

    Article  CAS  Google Scholar 

  • Bhattacharjee P, Paul S (2016) Risk of occupational exposure to asbestos, silicon and arsenic on pulmonary disorders: understanding the genetic-epigenetic interplay and future prospects. Environ Res 147:425–434

    Article  CAS  Google Scholar 

  • Boulanger G, Andujar P, Pairon JC, Billon-Galland MA, Dion C, Dumortier P, Brochard P, Sobaszek A, Bartsch P, Paris C (2014) Quantification of short and long asbestos fibers to assess asbestos exposure: a review of fiber size toxicity. Environ Health 13:1

    Article  CAS  Google Scholar 

  • Cardile V, Renis M, Scifo C, Lombardo L, Gulino R, Mancari B, Panico A (2004) Behaviour of the new asbestos amphibole fluoro-edenite in different lung cell systems. Int J Biochem Cell Biol 36:849–860

    Article  CAS  Google Scholar 

  • Cavallo D, Campopiano A, Cardinali G, Casciardi S, De Simone P, Kovacs D, Perniconi B, Spagnoli G, Ursini CL, Fanizza C (2004) Cytotoxic and oxidative effects induced by man-made vitreous fibers (MMVFs) in a human mesothelial cell line. Toxicology 201:219–229

    Article  CAS  Google Scholar 

  • Cely-Garcia MF, Torres-Duque CA, Duran M, Parada P, Sarmiento OL, Breysse PN, Ramos-Bonilla JP (2015) Personal exposure to asbestos and respiratory health of heavy vehicle brake mechanics. J Expo Sci Environ Epidemiol 25:26–36

    Article  Google Scholar 

  • Darcey DJ, Feltner C (2014) Occupational and environmental exposure to asbestos, pathology of asbestos-associated diseases. Springer, Berlin, Heidelberg, pp 11–24

  • Donaldson K, Murphy F, Schinwald A, Duffin R, Poland CA (2011) Identifying the pulmonary hazard of high aspect ratio nanoparticles to enable their safety-by-design. Nanomedicine 6:143–156

    Article  CAS  Google Scholar 

  • Fröhlich E (2012) The role of surface charge in cellular uptake and cytotoxicity of medical nanoparticles. Int J Nanomedicine 7:5577–5591

    Article  Google Scholar 

  • Fubini B, Mollo L, Giamello E (1995) Free radical generation at the solid/liquid interface in iron containing minerals. Free Radic Res 23:593–614

    Article  CAS  Google Scholar 

  • Funahashi S, Okazaki Y, Ito D, Asakawa A, Nagai H, Tajima M, Toyokuni S (2015) Asbestos and multi-walled carbon nanotubes generate distinct oxidative responses in inflammatory cells. J Clin Biochem Nutr 56:111–117

    Article  CAS  Google Scholar 

  • Gilmour PS, Brown DM, Beswick PH, MacNee W, Rahman I, Donaldson K (1997) Free radical activity of industrial fibers: role of iron in oxidative stress and activation of transcription factors. Environ Health Perspect 105:1313

    Article  CAS  Google Scholar 

  • Goodman JE, Peterson MK, Bailey LA, Kerper LE, Dodge DG (2014) Electricians’ chrysotile asbestos exposure from electrical products and risks of mesothelioma and lung cancer. Regul Toxicol Pharmacol 68:8–15

    Article  CAS  Google Scholar 

  • Guldberg M, Jensen SL, Knudsen T, Steenberg T, Kamstrup O (2002) High-alumina low-silica HT stone wool fibers: a chemical compositional range with high biosolubility. Regul Toxicol Pharmacol 35:217–226

    Article  CAS  Google Scholar 

  • Gulino GR, Polimeni M, Prato M, Gazzano E, Kopecka J, Colombatto S, Ghigo D, Aldieri E (2016) Effects of chrysotile exposure in human bronchial epithelial cells: insights into the pathogenic mechanisms of asbestos-related diseases. Environ Health Perspect 124:776

    Article  CAS  Google Scholar 

  • Guo H, Zhang J, Boudreau M, Meng J, Yin J, Liu J, Xu H (2016) Intravenous administration of silver nanoparticles causes organ toxicity through intracellular ROS-related loss of inter-endothelial junction. Part Fibre Toxicol 13:1

    Google Scholar 

  • Hoppe A, Güldal NS, Boccaccini AR (2011) A review of the biological response to ionic dissolution products from bioactive glasses and glass-ceramics. Biomaterials 32:2757–2774

    Article  CAS  Google Scholar 

  • Jargin SV (2015) Asbestos and its substitutes: international coordination and independent research needed. J Environ Occup Sci 4:1

    Article  Google Scholar 

  • Jiang L, Nagai H, Ohara H, Hara S, Tachibana M, Hirano S, Shinohara Y, Kohyama N, Akatsuka S, Toyokuni S (2008) Characteristics and modifying factors of asbestos-induced oxidative DNA damage. Cancer Sci 99:2142–2151

    Article  CAS  Google Scholar 

  • Ken DMBCF (1998) Free radical activity of synthetic vitreous fibers: iron chelation inhibits hydroxyl radical generation by refractory ceramic fiber. J Toxicol Environ Health Part A 53:545–561

    Article  Google Scholar 

  • Kim SY, Kim YC, Kim Y, Hong WH (2016) Predicting the mortality from asbestos-related diseases based on the amount of asbestos used and the effects of slate buildings in Korea. Sci Total Environ 542:1–11

    Article  CAS  Google Scholar 

  • Konecny R, Leonard S, Shi X, Robinson V, Castranova V (2001) Reactivity of free radicals on hydroxylated quartz surface and its implications for pathogenicity: experimental and quantum mechanical study. J Environ Pathol Toxicol Oncol Off Organ Int Soc Environ Toxicol Cancer 20(suppl 1):521–532

    Google Scholar 

  • Kusiorowski R, Zaremba T, Piotrowski J, Podwórny J (2015) Utilisation of cement-asbestos wastes by thermal treatment and the potential possibility use of obtained product for the clinker bricks manufacture. J Mater Sci 50:6757–6767

    Article  CAS  Google Scholar 

  • Lemos AT, Lemos CTD, Flores AN, Pantoja EO, Rocha JAV, Vargas VMF (2016) Genotoxicity biomarkers for airborne particulate matter (PM2.5) in an area under petrochemical influence. Chemosphere 159:610–618

    Article  CAS  Google Scholar 

  • Miozzi E, Rapisarda V, Marconi A, Costa C, Polito I, Spandidos DA, Libra M, Fenga C (2016) Fluoro-edenite and carbon nanotubes: the health impact of ‘asbestos-like’ fibres. Exp Ther Med 11:21–27

    Article  CAS  Google Scholar 

  • Murayama T, Takahashi K, Natori Y, Kurumatani N (2006) Estimation of future mortality from pleural malignant mesothelioma in Japan based on an age-cohort model. Am J Ind Med 49:1–7

    Article  Google Scholar 

  • Nagai H, Toyokuni S (2012) Differences and similarities between carbon nanotubes and asbestos fibers during mesothelial carcinogenesis: shedding light on fiber entry mechanism. Cancer Sci 103:1378–1390

    Article  CAS  Google Scholar 

  • Pacella A, Fantauzzi M, Turci F, Cremisini C, Montereali MR, Nardi E, Atzei D, Rossi A, Andreozzi GB (2015) Surface alteration mechanism and topochemistry of iron in tremolite asbestos: a step toward understanding the potential hazard of amphibole asbestos. Chem Geol 405:28–38

    Article  CAS  Google Scholar 

  • Pavan C, Tomatis M, Ghiazza M, Rabolli V, Bolis V, Lison D, Fubini B (2013) In search of the chemical basis of the hemolytic potential of silicas. Chem Res Toxicol 26:1188–1198

    Article  CAS  Google Scholar 

  • Pietrofesa RA, Velalopoulou A, Albelda SM, Christofidou-Solomidou M (2016) Asbestos induces oxidative stress and activation of Nrf2 signaling in murine macrophages: chemopreventive role of the synthetic lignan secoisolariciresinol diglucoside (LGM2605). Int J Mol Sci 17:322

    Article  CAS  Google Scholar 

  • Rapisarda V, Loreto C, Ledda C, Musumeci G, Bracci M, Santarelli L, Renis M, Ferrante M, Cardile V (2015) Cytotoxicity, oxidative stress and genotoxicity induced by glass fibers on human alveolar epithelial cell line A549. Toxicol In Vitro 29:551–557

    Article  CAS  Google Scholar 

  • Sadual RR, Badamali SK, Dapurkar SE, Singh RK (2015) Unusual oxidation behaviour of mesoporous silicates towards lignin model phenolic monomer. World J Nano Sci Eng 05:88–95

    Article  CAS  Google Scholar 

  • Sahmel J, Barlow CA, Gaffney S, Avens HJ, Madl AK, Henshaw J, Unice K, Galbraith D, DeRose G, Lee RJ (2016) Airborne asbestos take-home exposures during handling of chrysotile-contaminated clothing following simulated full shift workplace exposures. J Expo Sci Env Epid 26:48–62

    Article  CAS  Google Scholar 

  • Scarselli A, Corfiati M, Di Marzio D (2016) Occupational exposure in the removal and disposal of asbestos-containing materials in Italy. Int Arch Occup Environ Health 89:857–865

    Article  CAS  Google Scholar 

  • Schinwald A, Murphy F, Prina-Mello A, Poland C, Byrne F, Glass J, Dickerson J, Schultz D, Movia D, Jeffree C (2012) The threshold length for fibre-induced acute pleural inflammation: shedding light on the early events in asbestos-induced mesothelioma. Toxicol Sci 128:461–470

  • Sen S, Chakraborty R (2011) The role of antioxidants in human health. Oxidative stress: diagnostics, prevention, and therapy 1083, 1–37

  • Shukla A, Gulumian M, Hei TK, Kamp D, Rahman Q, Mossman BT (2003) Multiple roles of oxidants in the pathogenesis of asbestos-induced diseases. Free Radic Biol Med 34:1117–1129

    Article  CAS  Google Scholar 

  • Toyokuni S (1996) Iron-induced carcinogenesis: the role of redox regulation. Free Radic Biol Med 20(4):553–556

  • Toyokuni S (2014) Iron overload as a major targetable pathogenesis of asbestos-induced mesothelial carcinogenesis. Redox Rep 19:1–7

  • Utembe W, Potgieter K, Stefaniak AB, Gulumian M (2015) Dissolution and biodurability: important parameters needed for risk assessment of nanomaterials. Part Fibre Toxicol 12:1

    Article  CAS  Google Scholar 

  • Wang M, Dong F, Wang B, He X, Liu L, Sun S, Huo T (2015) Free radical generation at the solid/liquid interface in iron containing minerals. J Central South Univ (Science and Technology) 46:1967–1972

    CAS  Google Scholar 

  • Yu J, Liu S, Wu B, Shen Z, Cherr GN, Zhang X, Li M (2016) Comparison of cytotoxicity and inhibition of membrane ABC transporters induced by MWCNTs with different length and functional groups. Environ Sci Technol 50:3985–3994

    Article  CAS  Google Scholar 

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Acknowledgements

This study was founded by projects of the National Natural Science Foundation of China (41130746, 41602033 and 41472046). The authors would like to thank the preclinical medicine laboratory of Southwest Medical University for its support in the experiment. Specially, the authors would like to express heartfelt gratitude to Dr. Maarten A.T.M. Broekmans for his kind, patient, and valuable suggestions for this manuscript’s improvement.

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All authors contributed to this manuscript. Faqin Dong and Jianjun Deng conceived and designed the study. Tingting Huo, Wei Ye, and Pingping Wang performed the experiments. Wei Zhang performed the data analysis. Tingting Huo wrote this manuscript. Faqin Dong, Qingbi Zhang, and Dongping Sun guided the structure and contents of the paper and improved earlier drafts.

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Correspondence to Faqin Dong.

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Responsible editor: Philippe Garrigues

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Huo, T., Dong, F., Deng, J. et al. In vitro genotoxicity of asbestos substitutes induced by coupled stimulation of dissolved high-valence ions and oxide radicals. Environ Sci Pollut Res 25, 22356–22367 (2018). https://doi.org/10.1007/s11356-017-9796-5

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  • DOI: https://doi.org/10.1007/s11356-017-9796-5

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