PMID- 20570779
OWN - NLM
STAT- MEDLINE
DCOM- 20110503
LR  - 20211020
IS  - 1552-9924 (Electronic)
IS  - 0091-6765 (Print)
IS  - 0091-6765 (Linking)
VI  - 118
IP  - 11
DP  - 2010 Nov
TI  - Species-specific differential AhR expression protects human neural progenitor 
      cells against developmental neurotoxicity of PAHs.
PG  - 1571-7
LID - 10.1289/ehp.0901545 [doi]
AB  - BACKGROUND: Because of their lipophilicity, persistent organic pollutants (POPs) 
      cross the human placenta, possibly affecting central nervous system development. 
      Most POPs are known aryl hydrocarbon receptor (AhR) ligands and activators of AhR 
      signaling. Therefore, AhR activation has been suggested to cause developmental 
      neurotoxicity (DNT). OBJECTIVE: We studied the effects of AhR ligands on basic 
      processes of brain development in two comparative in vitro systems to determine 
      whether AhR-activation is the underlying mechanism for reported DNT of POPs in 
      humans. METHODS: We employed neurosphere cultures based on human neural 
      progenitor cells (hNPCs) and wild-type and AhR-deficient mouse NPCs (mNPCs) and 
      studied the effects of different AhR agonists [3-methylcholanthrene (3-MC), 
      benzo(a)pyrene [B(a)P], and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)] and an 
      antagonist [3'-methoxy-4'-nitroflavone (MNF)] on neurosphere development. 
      Moreover, we analyzed expression of AhR and genes involved in AhR signaling. 
      RESULTS: In contrast to wild-type mNPCs, hNPCs and AhR-deficient mNPCs were 
      insensitive to AhR agonism or antagonism. Although AhR modulation attenuated 
      wild-type mNPC proliferation and migration, hNPCs and AhR-deficient mNPCs 
      remained unaffected. Results also suggest that species-specific differences 
      resulted from nonfunctional AhR signaling in hNPCs. CONCLUSION: Our findings 
      suggest that in contrast to wild-type mNPCs, hNPCs were protected against 
      polycyclic aromatic hydrocarbon-induced DNT because of an absence of AhR This 
      difference may contribute to species-specific differences in sensitivity to POPs.
FAU - Gassmann, Kathrin
AU  - Gassmann K
AD  - Department of Molecular Toxicology, Institut fur umweltmedizinische Forschung 
      gGmbH, Heinrich Heine University, Dusseldorf, Germany.
FAU - Abel, Josef
AU  - Abel J
FAU - Bothe, Hanno
AU  - Bothe H
FAU - Haarmann-Stemmann, Thomas
AU  - Haarmann-Stemmann T
FAU - Merk, Hans F
AU  - Merk HF
FAU - Quasthoff, Kim N
AU  - Quasthoff KN
FAU - Rockel, Thomas Dino
AU  - Rockel TD
FAU - Schreiber, Timm
AU  - Schreiber T
FAU - Fritsche, Ellen
AU  - Fritsche E
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Environ Health Perspect
JT  - Environmental health perspectives
JID - 0330411
RN  - 0 (Environmental Pollutants)
RN  - 0 (Polychlorinated Dibenzodioxins)
RN  - 0 (Polycyclic Aromatic Hydrocarbons)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Aryl Hydrocarbon)
RN  - 3417WMA06D (Benzo(a)pyrene)
RN  - 56-49-5 (Methylcholanthrene)
SB  - IM
MH  - Animals
MH  - Benzo(a)pyrene/toxicity
MH  - Cells, Cultured
MH  - Environmental Pollutants/*toxicity
MH  - Gene Expression/drug effects
MH  - Humans
MH  - Methylcholanthrene/toxicity
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Nervous System/drug effects/growth & development/metabolism
MH  - Neurons/*drug effects/metabolism
MH  - Polychlorinated Dibenzodioxins/toxicity
MH  - Polycyclic Aromatic Hydrocarbons/*toxicity
MH  - RNA, Messenger/metabolism
MH  - Receptors, Aryl Hydrocarbon/genetics/*metabolism
MH  - Signal Transduction/drug effects
MH  - Species Specificity
MH  - Stem Cells/*drug effects/metabolism
PMC - PMC2974695
EDAT- 2010/06/24 06:00
MHDA- 2011/05/04 06:00
PMCR- 2010/11/01
CRDT- 2010/06/24 06:00
PHST- 2009/10/07 00:00 [received]
PHST- 2010/05/21 00:00 [revised]
PHST- 2010/06/22 00:00 [accepted]
PHST- 2010/06/24 06:00 [entrez]
PHST- 2010/06/24 06:00 [pubmed]
PHST- 2011/05/04 06:00 [medline]
PHST- 2010/11/01 00:00 [pmc-release]
AID - ehp-118-1571 [pii]
AID - 10.1289/ehp.0901545 [doi]
PST - ppublish
SO  - Environ Health Perspect. 2010 Nov;118(11):1571-7. doi: 10.1289/ehp.0901545.