Nanoparticle-Driven DNA Damage Mimics Irradiation-Related Carcinogenesis Pathways

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

^* To whom correspondence should be addressed. E-mail: robmroz{at}wp.pl.

	Abstract

The epidemiological association between cancer and exposure to ambient air pollution particles (PM₁₀) has been related to the ability of PM₁₀ and its constituent nanoparticles (NP) to cause reactive oxidative species (ROS)-driven DNA damage. However, there are no data on the molecular response to these genotoxic effects.

To assess whether PM₁₀, NP and ROS-driven DNA damage induces carcinogenesis pathways, A549 cells were treated with Tert-butyl-hyperperoxide (Tbh), Urban Dust (UD), Carbon Black, nanoparticulate CB (NPCB), benzo(a)pyrene and NPCB coated with BaP for up to 24 hours. DNA single and double strand breakage was determined by comet assay, cell cycle status was analyzed using flow cytometry. Nuclear extracts or acid-extracted histones were used for Western blot analysis of PSer15-p53, 53BP1, PH2A.X, and PBRCA1.

UD caused both single and double strand DNA breaks, whilst other tested NP caused only single strand DNA breaks. NP significantly altered cell cycle kinetics. Tbh enhanced PH2A.X after 1 and 6 hours (2.1 and 2.2 fold). NP increased 53BP1 expression at 1 hour (2.4–8.7 fold) and PBRCA1 at 1–6 hours. N-acetylcysteine blocked NP driven PSer15-p53 response.

NP and ROS induce DNA damage, activating p53 and proteins related to DNA repair, mimicking irradiation-related carcinogenesis pathways.

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