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Chem Biol Interact. 2010 Dec 5;188(3):558-65. doi: 10.1016/j.cbi.2010.09.014. Epub 2010 Sep 17.

Occurrence of molecular abnormalities of cell cycle in L132 cells after in vitro short-term exposure to air pollution PM(2.5).

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  • 1Université Lille Nord de France, Lille, France.

Abstract

To improve the knowledge of the underlying mechanisms implying in air pollution Particulate Matter (PM)-induced lung toxicity in humans, we were interested in the sequential occurrence of molecular abnormalities from TP53-RB gene signaling pathway activation in the L132 target human lung epithelial cell model. The most toxicologically relevant physical and chemical characteristics of air pollution PM(2.5) collected in Dunkerque, a French highly-industrialized sea-side city, were determined. L132 cells were exposed during 24, 48 and 72h to Dunkerque City's PM(2.5) (i.e. Lethal Concentration (LC)(10)=18.84μgPM/mL or 5.02μgPM/cm(2); LC(50)=75.36μgPM/mL or 20.10μgPM/cm(2)), TiO(2) and desorbed PM (i.e. dPM; EqLC(10)=15.42μg/mL or 4.11μgPM/cm(2); EqLC(50)=61.71μg/mL or 16.46μgPM/cm(2)), benzene (7μM) or Benzo[a]Pyrene (B[a]P; 1μM). Dunkerque City's PM(2.5) altered the gene expression and/or the protein concentration of several key cell cycle controllers from TP53-RB gene signaling pathway (i.e. P53; BCL2; P21; cyclin D1, cyclin-dependent kinase 1; retinoblastoma protein) in L132 cells, thereby leading to the occurrence of cell proliferation and apoptosis together. The activation of the critical cell cycle controllers under study might be related to PM-induced oxidative stress, through the possible involvement of covalent metals in redox systems, the metabolic activation of organic chemicals by enzyme-catalyzed reactions, and phagocytosis. Taken together, these results might ask the critical question whether there is a balance or, in contrast, rather an imbalance between the cell proliferation and the apoptosis occurring in PM-exposed L132 cells, with possible consequences in term of PM-induced lung tumorgenesis.

Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

PMID:
20850422
[PubMed - indexed for MEDLINE]
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