title: Airborne urban particles (Milan winter-PM2.5) cause mitotic arrest and cell death: Effects on DNA, mitochondria, AhR binding and spindle organization.
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.
authors.affiliation: Applied Cell Biology and Particles Effects, Department of Environmental Science, University Milano-Bicocca, Piazza della Scienza 1, 20126 Milano, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Gualtieri
authors.forename: Johan
authors.initials: J
authors.lastname: Ovrevik
authors.forename: Steen
authors.initials: S
authors.lastname: Mollerup
authors.forename: Nana
authors.initials: N
authors.lastname: Asare
authors.forename: Eleonora
authors.initials: E
authors.lastname: Longhin
authors.forename: Hans-Jørgen
authors.initials: HJ
authors.lastname: Dahlman
authors.forename: Marina
authors.initials: M
authors.lastname: Camatini
authors.forename: Jørn A
authors.initials: JA
authors.lastname: Holme
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects*; D006801:Humans; D008168:Lung / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects*; D008938:Mitosis / Q000187:drug effects*; D052638:Particulate Matter / Q000633:toxicity*; D012097:Repressor Proteins / Q000378:metabolism; D020545:Respiratory Mucosa / Q000187:drug effects; D008941:Spindle Apparatus / Q000187:drug effects*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D052638:Particulate Matter; D012097:Repressor Proteins; C492162:AHRR protein, human