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Airborne urban particles (Milan winter-PM2.5) cause mitotic arrest and cell death: Effects on DNA, mitochondria, AhR binding and spindle organization

TitoloAirborne urban particles (Milan winter-PM2.5) cause mitotic arrest and cell death: Effects on DNA, mitochondria, AhR binding and spindle organization
Tipo di pubblicazioneArticolo su Rivista peer-reviewed
Anno di Pubblicazione2011
AutoriGualtieri, Maurizio, Øvrevik J., Mollerup S., Asare N., Longhin E., Dahlman H.-J., Camatini M., and Holme J.A.
RivistaMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume713
Paginazione18-31
ISSN00275107
Parole chiaveairborne particle, aromatic hydrocarbon receptor, article, ATM protein, Basic Helix-Loop-Helix Transcription Factors, cell cycle arrest, cell damage, cell death, Cell Line, cell membrane, cell organelle, cell proliferation, cell viability, checkpoint kinase 2, chromosome, combustion, controlled study, cytochrome P450 1A1, cytochrome P450 1B1, DNA damage, DNA fragmentation, gene expression regulation, histone H2AX, histone phosphorylation, human, human cell, Humans, internalization, lung, Mitochondria, mitosis, mitosis inhibition, mitosis spindle, Mitotic Spindle Apparatus, particulate matter, priority journal, protein binding, protein phosphorylation, Repressor Proteins, Respiratory Mucosa
Abstract

Airborne particulate matter (PM) is considered to be an important contributor to lung diseases. In the present study we report that Milan winter-PM2.5 inhibited proliferation in human bronchial epithelial cells (BEAS-2B) by inducing mitotic arrest. The cell cycle arrest was followed by an increase in mitotic-apoptotic cells, mitotic slippage and finally an increase in "classical" apoptotic cells. Exposure to winter-PM10 induced only a slight effect which may be due to the presence of PM2.5 in this fraction while pure combustion particles failed to disturb mitosis. Fewer cells expressing the mitosis marker phospho-histone H3 compared to cells with condensed chromosomes, suggest that PM2.5 induced premature mitosis. PM2.5 was internalized into the cells and often localized in laminar organelles, although particles without apparent plasma membrane covering were also seen. In PM-containing cells mitochondria and lysosomes were often damaged, and in mitotic cells fragmented chromosomes often appeared. PM2.5 induced DNA strands breaks and triggered a DNA-damage response characterized by increased phosphorylation of ATM, Chk2 and H2AX; as well as induced a marked increase in expression of the aryl hydrocarbon receptor (AhR)-regulated genes, CYP1A1, CYP1B1 and AhRR. Furthermore, some disturbance of the organization of microtubules was indicated. It is hypothesized that the induced mitotic arrest and following cell death was due to a premature chromosome condensation caused by a combination of DNA, mitochondrial and spindle damage. © 2011 Elsevier B.V.

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URLhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-79960286112&doi=10.1016%2fj.mrfmmm.2011.05.011&partnerID=40&md5=3693e1dcaa9f263a79864cbf6086eee9
DOI10.1016/j.mrfmmm.2011.05.011
Citation KeyGualtieri201118