PMID- 17376491
OWN - NLM
STAT- MEDLINE
DCOM- 20070914
LR  - 20131121
IS  - 0027-5107 (Print)
IS  - 0027-5107 (Linking)
VI  - 621
IP  - 1-2
DP  - 2007 Aug 1
TI  - The environmental carcinogen benzo[a]pyrene induces expression of 
      monocyte-chemoattractant protein-1 in vascular tissue: a possible role in 
      atherogenesis.
PG  - 31-41
AB  - Exposure to carcinogenic polycyclic aromatic hydrocarbons (PAHs) has been 
      implicated in the aetiology of atherosclerosis. Previously we showed that chronic 
      exposure of ApoE-/- mice to the prototype PAH benzo[a]pyrene (B[a]P) causes 
      enhanced progression of atherosclerosis, which was characterised by an increased 
      inflammatory cell content in the atherosclerotic plaques. The aim of the present 
      study was to evaluate the effect of B[a]P on vascular expression of 
      monocyte-chemoattractant protein 1 (MCP-1), which is a crucial molecule promoting 
      the recruitment of monocytes into atherosclerotic lesions. We hypothesised that 
      B[a]P-induced expression of MCP-1 is mediated through aryl hydrocarbon receptor 
      (AhR) activation. Initially we performed in vivo studies showing that acute 
      treatment with B[a]P induces MCP-1 gene expression in aortic tissue of ApoE-/- 
      mice. These observations could be confirmed by in vitro studies with human 
      endothelial cells (RF24 cell line and primary HUVEC), showing a dose- and 
      time-dependent increase in MCP-1 expression upon exposure to B[a]P. This was 
      paralleled by an induction of cytochrome P450 1A1 and 1B1, indicating Ah receptor 
      activation. No increased gene expression (MCP-1, CYP1A1 and 1B1) was found upon 
      incubation with the structural isomer benzo[e]pyrene, which is a weak AhR 
      agonist. Moreover, B[a]P-induced MCP-1 gene and protein expression was inhibited 
      by co-treatment with the AhR antagonist alpha-naphthoflavone. In addition to its 
      effect on basal gene expression, we showed that B[a]P significantly enhanced 
      TNFalpha-induced expression of MCP-1. We were unable to block B[a]P-induced MCP-1 
      expression by antioxidant treatment. In contrast, we found that addition of 
      N-acetylcysteine or vitamin C enhanced transcription of MCP-1 by B[a]P. In 
      conclusion, our studies revealed potent vascular pro-inflammatory effects of 
      B[a]P, as evidenced by AhR-mediated induction of MCP-1. These observations 
      further contribute to the concept that induction of inflammation is a crucial 
      process in PAH-enhanced atherogenesis.
FAU - Knaapen, Ad M
AU  - Knaapen AM
AD  - Department of Health Risk Analysis and Toxicology, Nutrition and Toxicology 
      Research Institute Maastricht (NUTRIM), The Netherlands. 
      a.knaapen@grat.unimaas.nl
FAU - Curfs, Danielle M
AU  - Curfs DM
FAU - Pachen, Danielle M
AU  - Pachen DM
FAU - Gottschalk, Ralph W
AU  - Gottschalk RW
FAU - de Winther, Menno P J
AU  - de Winther MP
FAU - Daemen, Mat J
AU  - Daemen MJ
FAU - Van Schooten, Frederik J
AU  - Van Schooten FJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070228
PL  - Netherlands
TA  - Mutat Res
JT  - Mutation research
JID - 0400763
RN  - 0 (Apolipoproteins E)
RN  - 0 (Carcinogens, Environmental)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Receptors, Aryl Hydrocarbon)
RN  - 3417WMA06D (Benzo(a)pyrene)
SB  - IM
MH  - Animals
MH  - Aorta, Thoracic/*drug effects/metabolism
MH  - Apolipoproteins E/genetics
MH  - Atherosclerosis/blood/*chemically induced/metabolism
MH  - Benzo(a)pyrene/*toxicity
MH  - Carcinogens, Environmental/*toxicity
MH  - Cell Line
MH  - Cell Survival/drug effects
MH  - Chemokine CCL2/*biosynthesis/genetics
MH  - Endothelial Cells/*drug effects/metabolism
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Flow Cytometry
MH  - Gene Expression/drug effects
MH  - Humans
MH  - Leukocyte Count
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Oxidative Stress/drug effects
MH  - Receptors, Aryl Hydrocarbon/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
EDAT- 2007/03/23 09:00
MHDA- 2007/09/15 09:00
CRDT- 2007/03/23 09:00
PHST- 2006/08/23 00:00 [received]
PHST- 2006/12/12 00:00 [revised]
PHST- 2006/12/13 00:00 [accepted]
PHST- 2007/03/23 09:00 [pubmed]
PHST- 2007/09/15 09:00 [medline]
PHST- 2007/03/23 09:00 [entrez]
AID - S0027-5107(07)00084-X [pii]
AID - 10.1016/j.mrfmmm.2006.12.010 [doi]
PST - ppublish
SO  - Mutat Res. 2007 Aug 1;621(1-2):31-41. doi: 10.1016/j.mrfmmm.2006.12.010. Epub 
      2007 Feb 28.