HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Mroz, R. M. Articles by Donaldson, K. PubMed PubMed Citation Articles by Mroz, R. M. Articles by Donaldson, K.

Nanoparticle-driven DNA damage mimics irradiation-related carcinogenesis pathways

¹ ELEGI/Colt Laboratories, University of Edinburgh, Edinburgh, Scotland, UK. ² Pneumology Dept, and ⁴ Dept of Clinical Pharmacology, Medical University of Bialystok, Bialystok, Poland. ³ Institut für umweltmedizinische Forschung, Heinrich-Heine-University, Düsseldorf, Germany.

CORRESPONDENCE: R. M. Mroz, Pneumology Dept, Medical University of Bialystok, Ul. Zurawia 14, Bialystok, Poland. Fax: 48 857324149. E-mail: robmroz{at}wp.pl

Keywords: DNA damage, H2A.X histone, nanoparticles, particles with a 50% cut-off aerodynamic diameter of 10µm, reactive oxidative species

Received: January 18, 2007
Accepted November 13, 2007

The epidemiological association between cancer and exposure to ambient air pollution particles (particles with a 50% cut-off aerodynamic diameter of 10 µm (PM₁₀)) has been related to the ability of PM₁₀ 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 PM₁₀, 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 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.