PMID- 18554780
OWN - NLM
STAT- MEDLINE
DCOM- 20081014
LR  - 20161124
IS  - 1872-7980 (Electronic)
IS  - 0304-3835 (Linking)
VI  - 270
IP  - 1
DP  - 2008 Oct 18
TI  - Genotoxic potential of Polycyclic Aromatic Hydrocarbons-coated onto airborne 
      Particulate Matter (PM 2.5) in human lung epithelial A549 cells.
PG  - 144-55
LID - 10.1016/j.canlet.2008.04.044 [doi]
AB  - To improve the knowledge of the underlying mechanisms of action involved in air 
      pollution Particulate Matter (PM)-induced toxicity in human lungs, with a 
      particular interest of the crucial role played by coated-organic chemicals, we 
      were interested in the metabolic activation of Polycyclic Aromatic Hydrocarbons 
      (PAH)-coated onto air pollution PM, and, thereafter, the formation of PAH-DNA 
      adducts in a human lung epithelial cell model (A549 cell line). Cells were 
      exposed to Dunkerque city's PM(2.5) at its Lethal Concentrations at 10% and 50% 
      (i.e. LC(10)=23.72 microg/mL or 6.33 microg/cm2, and LC(50)=118.60 microg/mL or 
      31.63 microg/cm2), and the study of Cytochrome P450 (CYP) 1A1 gene expression 
      (i.e. RT-PCR) and protein activity (i.e. EROD activity), and the formation of 
      PAH-DNA adducts (i.e. 32P-postlabeling), were investigated after 24, 48, and/or 
      72 h. PAH, PolyChlorinated Dibenzo-p-Dioxins and -Furans (PCDD/F), Dioxin-Like 
      PolyChlorinated Biphenyls (DLPCB), and PolyChlorinated Biphenyls (PCB)-coated 
      onto collected PM were determined (i.e. GC/MS and HRGC/HRMS, respectively), 
      Negative (i.e. TiO2 or desorbed PM, dPM; EqLC10=19.42 microg/mL or 5.18 
      microg/cm2, and EqLC50=97.13 microg/mL or 25.90 microg/cm2), and positive (i.e. 
      benzo(a)pyrene; 1 microM) controls were included in the experimental design. 
      Statistically significant increases of CYP1A1 gene expression and protein 
      activity were observed in A549 cells, 24, 48 and 72 h after their exposure to 
      dPM, suggesting thereby that the employed outgassing method was not efficient 
      enough to remove total PAH. Both the CYP1A1 gene expression and EROD activity 
      were highly induced 24, 48 and 72 h after cell exposure to PM. However, only very 
      low levels of PAH-DNA adducts, also not reliably quantifiable, were reported 72 h 
      after cell exposure to dPM, and, particularly, PM. The relatively low levels of 
      PAH together with the presence of PCDD/F, DLPCB, and PCB-coated onto Dunkerque 
      City's PM 2.5 could notably contribute to explain the borderline detection of 
      PAH-DNA adducts in dPM and/or PM-exposed A549 cells. Hence, remaining very low 
      doses of PAH in dPM or relatively low doses of PAH-coated onto PM were involved 
      in enzymatic induction, a key feature in PAH-toxicity, but failed to show a clear 
      genotoxicity in this in vitro study. We also concluded that, in the human lung 
      epithelial cell model we used, and in the experimental conditions we chose, 
      bulky-DNA adduct formation was apparently not a major factor involved in the 
      Dunkerque City's PM 2.5-induced toxicity.
FAU - Billet, Sylvain
AU  - Billet S
AD  - LCE EA 2598, Toxicologie Industrielle et Environnementale, Universite du Littoral 
      - Cote d'Opale, Maison de la Recherche en Environnement Industriel de Dunkerque 
      2, 189A, Avenue Maurice Schumann, 59140 Dunkerque, France.
FAU - Abbas, Imane
AU  - Abbas I
FAU - Le Goff, Jeremie
AU  - Le Goff J
FAU - Verdin, Anthony
AU  - Verdin A
FAU - Andre, Veronique
AU  - Andre V
FAU - Lafargue, Paul-Eric
AU  - Lafargue PE
FAU - Hachimi, Adam
AU  - Hachimi A
FAU - Cazier, Fabrice
AU  - Cazier F
FAU - Sichel, Francois
AU  - Sichel F
FAU - Shirali, Pirouz
AU  - Shirali P
FAU - Garcon, Guillaume
AU  - Garcon G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080612
PL  - Ireland
TA  - Cancer Lett
JT  - Cancer letters
JID - 7600053
RN  - 0 (DNA Adducts)
RN  - 0 (Particulate Matter)
RN  - 0 (Polychlorinated Dibenzodioxins)
RN  - 0 (Polycyclic Aromatic Hydrocarbons)
RN  - 0 (polycyclic aromatic hydrocarbons-DNA adduct)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP1A1)
SB  - IM
MH  - Cytochrome P-450 CYP1A1/analysis/genetics/*physiology
MH  - DNA Adducts/*metabolism
MH  - Epithelial Cells/drug effects
MH  - Humans
MH  - Lung/*drug effects
MH  - Lung Neoplasms/*etiology
MH  - Particulate Matter/*toxicity
MH  - Polychlorinated Dibenzodioxins/analogs & derivatives/toxicity
MH  - Polycyclic Aromatic Hydrocarbons/metabolism/*toxicity
EDAT- 2008/06/17 09:00
MHDA- 2008/10/15 09:00
CRDT- 2008/06/17 09:00
PHST- 2008/01/29 00:00 [received]
PHST- 2008/04/29 00:00 [revised]
PHST- 2008/04/29 00:00 [accepted]
PHST- 2008/06/17 09:00 [pubmed]
PHST- 2008/10/15 09:00 [medline]
PHST- 2008/06/17 09:00 [entrez]
AID - S0304-3835(08)00356-X [pii]
AID - 10.1016/j.canlet.2008.04.044 [doi]
PST - ppublish
SO  - Cancer Lett. 2008 Oct 18;270(1):144-55. doi: 10.1016/j.canlet.2008.04.044. Epub 
      2008 Jun 12.