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Combined toxic effect of airborne heavy metals on human lung cell line A549

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Abstract

Many studies have demonstrated that heavy metals existing as a mixture in the atmospheric environment cause adverse effects on human health and are important key factors of cytotoxicity; however, little investigation has been conducted on a toxicological study of a metal mixture from atmospheric fine particulate matter. The objective of this study was to predict the combined effects of heavy metals in aerosol by using in vitro human cells and obtain a suitable mixture toxicity model. Arsenic, nickel, and lead were selected for mixtures exposed to A549 human lung cancer cells. Cell proliferation (WST-1), glutathione (GSH), and interleukin (IL)-8 inhibition were observed and applied to the prediction models of mixture toxicity, concentration addition (CA) and independent action (IA). The total mixture concentrations were set by an IC10-fixed ratio of individual toxicity to be more realistic for mortality and enzyme inhibition tests. The results showed that the IA model was statistically closer to the observed results than the CA model in mortality, indicating dissimilar modes of action. For the GSH inhibition, the results predicted by the IA and CA models were highly overestimated relative to mortality. Meanwhile, the IL-8 results were stable with no significant change in immune reaction related to inflammation. In conclusion, the IA model is a rapid prediction model in heavy metals mixtures; mortality, as a total outcome of cell response, is a good tool for demonstrating the combined toxicity rather than other biochemical responses.

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References

  • Adamson, I. Y., Prieditis, H., & Vincent, R. (1999). Pulmonary toxicity of an atmospheric particulate sample is due to the soluble fraction. Toxicology and Applied Pharmacology, 157(1), 43–50.

    Article  CAS  Google Scholar 

  • Ahamed, M., & Siddiqui, M. K. J. (2007). Environmental lead toxicity and nutritional factors. Clinical Nutrition, 26(4), 400–408.

    Article  CAS  Google Scholar 

  • Altenburger, R., Backhaus, T., Boedeker, W., Faust, M., Scholze, M., & Grimme, L. H. (2000). Predictability of the toxicity of multiple chemical mixtures to Vibrio fischeri: Mixtures composed of similarly acting chemicals. Environmental Toxicology and Chemistry, 19(9), 2341–2347.

    Article  CAS  Google Scholar 

  • Backhaus, T., Altenburger, R., Boedeker, W., Faust, M., Scholze, M., & Grimme, L. H. (2000). Predictability of the toxicity of a multiple mixture of dissimilarly acting chemicals to Vibrio fischeri. Environmental Toxicology and Chemistry, 19(9), 2348–2356.

    Article  CAS  Google Scholar 

  • Bakand, S., Winder, C., Khalil, C., & Hayes, A. (2005). Toxicity assessment of industrial chemicals and airborne contaminants: Transition from in vivo to in vitro test methods: a review. Inhalation Toxicology, 17(13), 775–787.

    Article  CAS  Google Scholar 

  • Barchowsky, A., Dudek, E. J., Treadwell, M. D., & Wetterhahn, K. E. (1996). Arsenic induces oxidant stress and NF-kB activation in cultured aortic endothelial cells. Free Radical Biology and Medicine, 21(6), 783–790.

    Article  CAS  Google Scholar 

  • Bernhoft, A., Keblys, M., Morrison, E., Larsen, H. J. S., & Flåøyen, A. (2004). Combined effects of selected Penicillium mycotoxins on in vitro proliferation of porcine lymphocytes. Mycopathologia, 158(4), 441–450.

    Article  CAS  Google Scholar 

  • Cancer, I. A. f. R. o. (2004). Certain polycyclic aromatic hydrocarbons and heterocyclic compounds. IARC monographs on the evaluation of the carcinogenic risks of chemicals to man, 3.

  • Cao, S., Duan, X., Zhao, X., Ma, J., Dong, T., Huang, N., et al. (2014). Health risks from the exposure of children to As, Se, Pb and other heavy metals near the largest coking plant in China. Science of the Total Environment, 472, 1001–1009.

    Article  CAS  Google Scholar 

  • Costa, D. L., & Dreher, K. L. (1997). Bioavailable transition metals in particulate matter mediate cardiopulmonary injury in healthy and compromised animal models. Environmental Health Perspectives, 105(Suppl 5), 1053.

    Article  Google Scholar 

  • da Silva, D. D., Silva, E., & Carmo, H. (2013). Cytotoxic effects of amphetamine mixtures in primary hepatocytes are severely aggravated under hyperthermic conditions. Toxicology in Vitro, 27(6), 1670–1678.

    Article  Google Scholar 

  • Davidson, C. I., Phalen, R. F., & Solomon, P. A. (2005). Airborne particulate matter and human health: A review. Aerosol Science and Technology, 39(8), 737–749.

    Article  CAS  Google Scholar 

  • Denkhaus, E., & Salnikow, K. (2002). Nickel essentiality, toxicity, and carcinogenicity. Critical Reviews in Oncology/Hematology, 42(1), 35–56.

    Article  CAS  Google Scholar 

  • Dominici, F., Peng, R. D., Ebisu, K., Zeger, S. L., Samet, J. M., & Bell, M. L. (2007). Does the effect of PM10 on mortality depend on PM nickel and vanadium content? A reanalysis of the NMMAPS data. Environmental Health Perspectives, 115(12), 1701–1703.

  • Dyer, S., Warne, S. J., Meyer, J. S., Leslie, H. A., & Escher, B. I. (2011). Tissue residue approach for chemical mixtures. Integrated Environmental Assessment and Management, 7(1), 99–115.

    Article  CAS  Google Scholar 

  • Engell-Kofoed, A. E. (2005). Single substance and mixture toxicity of three toxicants with similar and dissimilar modes of action to Daphnia magna. Master Thesis Thesis, Roskilde University, Roskilde,

  • Farley, K. J., & Meyer, J. S. (2015). Metal mixture modeling evaluation project: 3. Lessons learned and steps forward. Environmental Toxicology and Chemistry, 34(4), 821–832.

    Article  CAS  Google Scholar 

  • Filep, Á., Drinovec, L., Palágyi, A., Manczinger, L., Vágvölgyi, C., Bozóki, Z., et al. (2015). Source specific cyto-and genotoxicity of atmospheric aerosol samples. Aerosol and Air Quality Research, 15(6S), 2325–2331.

    CAS  Google Scholar 

  • Franklin, M., Koutrakis, P., & Schwartz, J. (2008). The role of particle composition on the association between PM2. 5 and mortality. Epidemiology (Cambridge, Mass.), 19(5), 680.

    Article  Google Scholar 

  • Harrison, R. M., & Yin, J. (2000). Particulate matter in the atmosphere: which particle properties are important for its effects on health? Science of the Total Environment, 249(1), 85–101.

    Article  CAS  Google Scholar 

  • Hermens, J., Busser, F., Leeuwangh, P., & Musch, A. (1985). Quantitative structure–activity relationships and mixture toxicity of organic chemicals in Photobacterium phosphoreum: the Microtox test. Ecotoxicology and Environmental Safety, 9(1), 17–25.

    Article  CAS  Google Scholar 

  • Imrich, C.-A. W. G. A., & Ning, H. D. Y. (1998). Analysis of air pollution particulate-mediated oxidant stress in alveolar macrophages. Journal of Toxicology and Environmental Health Part A, 54(7), 529–545.

    Article  Google Scholar 

  • Jho, E. H., An, J., & Nam, K. (2011). Extended biotic ligand model for prediction of mixture toxicity of Cd and Pb using single metal toxicity data. Environmental Toxicology and Chemistry, 30(7), 1697–1703.

    Article  CAS  Google Scholar 

  • Kelly, F. J., & Fussell, J. C. (2012). Size, source and chemical composition as determinants of toxicity attributable to ambient particulate matter. Atmospheric Environment, 60, 504–526.

    Article  CAS  Google Scholar 

  • Le Tertre, A., Medina, S., Samoli, E., Forsberg, B., Michelozzi, P., Boumghar, A., et al. (2002). Short-term effects of particulate air pollution on cardiovascular diseases in eight European cities. Journal of Epidemiology and Community Health, 56(10), 773–779.

    Article  Google Scholar 

  • Lewtas, J. (2007). Air pollution combustion emissions: characterization of causative agents and mechanisms associated with cancer, reproductive, and cardiovascular effects. Mutation Research/Reviews in Mutation Research, 636(1), 95–133.

    Article  CAS  Google Scholar 

  • Maciejczyk, P., & Chen, L. C. (2005). Effects of subchronic exposures to concentrated ambient particles (CAPs) in mice: VIII. Source-related daily variations in in vitro responses to CAPs. Inhalation Toxicology, 17(4–5), 243–253.

    Article  CAS  Google Scholar 

  • Meyer, J. S., Ranville, J. F., Pontasch, M., Gorsuch, J. W., & Adams, W. J. (2015). Acute toxicity of binary and ternary mixtures of Cd, Cu, and Zn to Daphnia magna. Environmental Toxicology and Chemistry, 34(4), 799–808.

    Article  CAS  Google Scholar 

  • Paur, H.-R., Cassee, F. R., Teeguarden, J., Fissan, H., Diabate, S., Aufderheide, M., et al. (2011). In-vitro cell exposure studies for the assessment of nanoparticle toxicity in the lung—A dialog between aerosol science and biology. Journal of Aerosol Science, 42(10), 668–692.

    Article  CAS  Google Scholar 

  • Pavagadhi, S., Betha, R., Venkatesan, S., Balasubramanian, R., & Hande, M. P. (2013). Physicochemical and toxicological characteristics of urban aerosols during a recent Indonesian biomass burning episode. Environmental Science and Pollution Research, 20(4), 2569–2578.

    Article  CAS  Google Scholar 

  • Pope, C. A., Burnett, R. T., Thurston, G. D., Thun, M. J., Calle, E. E., Krewski, D., et al. (2004). Cardiovascular mortality and long-term exposure to particulate air pollution epidemiological evidence of general pathophysiological pathways of disease. Circulation, 109(1), 71–77.

    Article  Google Scholar 

  • Ra, J. S., Lee, B. C., Chang, N. I., & Kim, S. D. (2006). Estimating the combined toxicity by two-step prediction model on the complicated chemical mixtures from wastewater treatment plant effluents. Environmental Toxicology and Chemistry, 25(8), 2107–2113.

    Article  CAS  Google Scholar 

  • Roemer, W., Hoek, G., Brunekreef, B., Clench-Aas, J., Forsberg, B., Pekkanen, J., et al. (2000). PM10 elemental composition and acute respiratory health effects in European children (PEACE project). Pollution Effects on Asthmatic Children in Europe. European Respiratory Journal, 15(3), 553–559.

    Article  CAS  Google Scholar 

  • Salem, H., & Katz, S. A. (2005). Inhalation Toxicology (2nd ed.). Boca Raton: CRC Press.

    Google Scholar 

  • Satarug, S., Baker, J. R., Urbenjapol, S., Haswell-Elkins, M., Reilly, P. E. B., Williams, D. J., & Moore, M. R. (2003). A global perspective on cadmium pollution and toxicity in non-occupationally exposed population. Toxicology Letters, 137(1–2), 65–83.

    Article  CAS  Google Scholar 

  • Shi, H., Shi, X., & Liu, K. J. (2004). Oxidative mechanism of arsenic toxicity and carcinogenesis. Molecular and Cellular Biochemistry, 255(1–2), 67–78.

    Article  CAS  Google Scholar 

  • Valavanidis, A., Fiotakis, K., & Vlachogianni, T. (2008). Airborne particulate matter and human health: Toxicological assessment and importance of size and composition of particles for oxidative damage and carcinogenic mechanisms. Journal of Environmental Science and Health, Part C, 26(4), 339–362.

    Article  CAS  Google Scholar 

  • van Gestel, C. A., Jonker, M., Kammenga, J. E., Laskowski, R., & Svendsen, C. (2010). Mixture toxicity: Linking approaches from ecological and human toxicology: CRC press.

  • Warne, M. S. J., & van Dam, R. (2008). NOEC and LOEC data should no longer be generated or used. Australasian Journal of Ecotoxicology, 14(1), 1.

    Google Scholar 

  • Xu, X., Li, Y., Wang, Y., & Wang, Y. (2011). Assessment of toxic interactions of heavy metals in multi-component mixtures using sea urchin embryo-larval bioassay. Toxicology in Vitro, 25(1), 294–300.

    Article  Google Scholar 

  • Zhao, H., Xia, B., Fan, C., Zhao, P., & Shen, S. (2012). Human health risk from soil heavy metal contamination under different land uses near Dabaoshan Mine, Southern China. Science of the Total Environment, 417, 45–54.

    Article  Google Scholar 

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Acknowledgements

This study was funded by “PM2.5 research center supported by Ministry of Science, ICT, and Future Planning (MSIP) and National Research Foundation (NRF) of Korea (2014M3C8A5030618)”.

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Correspondence to Sang D. Kim.

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Choi, Y., Park, K., Kim, I. et al. Combined toxic effect of airborne heavy metals on human lung cell line A549. Environ Geochem Health 40, 271–282 (2018). https://doi.org/10.1007/s10653-016-9901-6

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  • DOI: https://doi.org/10.1007/s10653-016-9901-6

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