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Eur Respir J. 2008 Feb;31(2):241-51. Epub 2007 Dec 5.

Nanoparticle-driven DNA damage mimics irradiation-related carcinogenesis pathways.

Author information

1
ELEGI/Colt Laboratories, University of Edinburgh, Edinburgh, Scotland, UK. robmroz@wp.pl

Abstract

The epidemiological association between cancer and exposure to ambient air pollution particles (particles with a 50% cut-off aerodynamic diameter of 10 microm (PM(10))) has been related to the ability of PM(10) and its constituent nanoparticles (NPs) to cause reactive oxidative species (ROS)-driven DNA damage. However, there are no data on the molecular response to these genotoxic effects. In order to assess whether PM(10), NP and ROS-driven DNA damage induce carcinogenesis pathways, A549 cells were treated with tert-butyl-hyperperoxide (Tbh), urban dust (UD), carbon black (CB), nanoparticulate CB (NPCB), benzo(a)pyrene (BaP) and NPCB coated with BaP for <or=24 h. Single- and double-strand breakage of DNA was determined by comet assay; cell cycle status was analysed using flow cytometry. Nuclear extracts or acid-extracted histones were used for Western blot analysis of p-ser15-p53 (p53 phosphorylated at ser15), p53 binding protein (53BP) 1, phospho-histone H2A.X (p-H2A.X) and phospho-BRCA1 (p-BRCA1). UD caused both single- and double-strand DNA breaks, while other tested NPs caused only single-strand DNA breaks. NPs significantly altered cell cycle kinetics. Tbh enhanced p-H2A.X after 1 and 6 h (2.1- and 2.2-fold, respectively). NP increased 53BP1 expression at 1 h (2.4-8.7-fold) and p-BRCA1 at 1-6 h. N-acetylcysteine blocked NP-driven p-ser15-p53 response. In conclusion, nanoparticles and reactive oxidative species induce DNA damage, activating p53 and proteins related to DNA repair, mimicking irradiation-related carcinogenesis pathways.

PMID:
18057054
DOI:
10.1183/09031936.00006707
[Indexed for MEDLINE]
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