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Soluble metals as well as the insoluble particle fraction are involved in cellular DNA damage induced by particulate matter

  • Chapter
Oxygen/Nitrogen Radicals: Cell Injury and Disease

Part of the book series: Developments in Molecular and Cellular Biochemistry ((DMCB,volume 37))

Abstract

Exposure to ambient particulate matter has been reported to be associated with increased rates of lung cancer. Previously we showed that total suspended particulate matter (PM) induces oxidative DNA damage in epithelial lung cells. The aim of the present study was to further investigate the mechanism of PM-induced DNA damage, in which soluble iron-mediated hydroxyl radical (’OH) formation is thought to play a crucial role. Using electron spin resonance (ESR) we showed that PM suspensions as well as their particle-free, water-soluble fractions can generate ‘OH in the presence of hydrogen peroxide (H202), an effect which was abrogated by both deferoxamine and catalase. In addition, PM was also found to induce the ‘OH-specific DNA lesion 8-hydroxydeoxyguanosine (8-OHdG) in the presence of H2O2 as assessed by dot-blot analysis of calf thymus DNA using an 8-OHdG antibody. In human alveolar epithelial cells (A549), both PM suspensions and the particle-free soluble fraction elicited formation of DNA strand breaks (comet-assay). Unlike the acellular DNA assays, in epithelial cells the DNA-damaging capacity of the particle suspensions appeared to be stronger than that of their corresponding particle-free filtrates. In conclusion, our findings demonstrate that the water-soluble fraction of PM elicits DNA damage via transition metal-dependent ‘OH formation, implicating an important role of H202. Moreover, our data indicate that direct `particle’ effects contribute to the genotoxic hazard of ambient particulate matter in lung target cells. (Mol Cell Biochem 234/235: 317-326, 2002)

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Authors and Affiliations

  1. Research Institute for Environmental Health (IUF), Particle Research Core, Düsseldorf, Germany

    Ad M. Knaapen, Tingming Shi, Paul J.A. Borm & Roel P.F. Schins

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  1. Ad M. Knaapen
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  2. Tingming Shi
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  3. Paul J.A. Borm
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  4. Roel P.F. Schins
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Editors and Affiliations

  1. Pathology and Physiology Research Branch, National Institute for Occupational Safety and Health, 1095 Willowdale Road Mall Stop B167, Morgantown, WV, 26505, USA

    Val Vallyathan , Xianglin Shi Ph.D.  & Vince Castranova ,  & 

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Knaapen, A.M., Shi, T., Borm, P.J., Schins, R.P. (2002). Soluble metals as well as the insoluble particle fraction are involved in cellular DNA damage induced by particulate matter. In: Vallyathan, V., Shi, X., Castranova, V. (eds) Oxygen/Nitrogen Radicals: Cell Injury and Disease. Developments in Molecular and Cellular Biochemistry, vol 37. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-1087-1_36

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  • DOI: https://doi.org/10.1007/978-1-4615-1087-1_36

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-5388-1

  • Online ISBN: 978-1-4615-1087-1

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