PMID- 16033994
OWN - NLM
STAT- MEDLINE
DCOM- 20051207
LR  - 20161124
IS  - 1096-6080 (Print)
IS  - 1096-0929 (Linking)
VI  - 87
IP  - 2
DP  - 2005 Oct
TI  - Coplanar polychlorinated biphenyls activate the aryl hydrocarbon receptor in 
      developing tissues of two TCDD-responsive lacZ mouse lines.
PG  - 529-36
AB  - In utero exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) can have an 
      immediate impact on developmental processes that then lead to long-term deficits 
      in function. To define the specific tissues affected by TCDD during development, 
      we developed a lacZ-reporter gene mouse model driven by activation of the aryl 
      hydrocarbon receptor (AhR). Exposure to TCDD on gestational day (GD) 14 results 
      in strong activation of the lacZ transgene in numerous tissues including fore and 
      hind paws, ear, and genital tubercle. Experiments were conducted to examine the 
      ability of alternative AhR ligands to activate our model system. The coplanar 
      polychlorinated biphenyl congeners 3,4,5,3',4'-pentachlorobiphenyl (PCB126) and 
      3,4,3',4'-tetrachlorobiphenyl (PCB77) both induced staining in fetal tissues 
      identical to that observed following TCDD exposure. Exposure of fetuses to the 
      PCB mixture Aroclor 1254 and the non-coplanar congener 
      2,3,6,2',5'-pentachlorobiphenyl (PCB95) did not result in any activation of the 
      lacZ transgene. In addition to the testing of alternative ligands, another line 
      of reporter mice was generated to determine the potential influence of the site 
      of insertion of the lacZ transgene on the reported observations. Both TCDD and 
      the coplanar PCBs induced a similar pattern of staining in the new line as 
      compared to that observed in the original lacZ reporter mouse line. The ability 
      of AhR ligands, other than TCDD, to activate the AhR-mediated transgene, in 
      combination with the insertion-site independence of the response, strengthens the 
      data previously derived from this model and increases the utility of this system 
      for investigations examining AhR-mediated events during development.
FAU - Bemis, Jeffrey C
AU  - Bemis JC
AD  - Department of Environmental Medicine, University of Rochester School of Medicine 
      and Dentistry, New York 14642, USA.
FAU - Nazarenko, Daniel A
AU  - Nazarenko DA
FAU - Gasiewicz, Thomas A
AU  - Gasiewicz TA
LA  - eng
GR  - ES01247/ES/NIEHS NIH HHS/United States
GR  - ES07026/ES/NIEHS NIH HHS/United States
GR  - ES09430/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20050720
PL  - United States
TA  - Toxicol Sci
JT  - Toxicological sciences : an official journal of the Society of Toxicology
JID - 9805461
RN  - 0 (DNA Transposable Elements)
RN  - 0 (Environmental Pollutants)
RN  - 0 (Polychlorinated Dibenzodioxins)
RN  - 0 (Receptors, Aryl Hydrocarbon)
RN  - DFC2HB4I0K (Polychlorinated Biphenyls)
RN  - EC 3.2.1.23 (beta-Galactosidase)
SB  - IM
MH  - Animals
MH  - Biotransformation/drug effects
MH  - Cell Line
MH  - DNA Transposable Elements
MH  - Environmental Pollutants/*toxicity
MH  - Female
MH  - Fetus/pathology
MH  - Gene Expression Regulation, Enzymologic/drug effects
MH  - Lac Operon/*drug effects
MH  - Mice
MH  - Polychlorinated Biphenyls/*chemistry/*toxicity
MH  - Polychlorinated Dibenzodioxins/*toxicity
MH  - Pregnancy
MH  - Receptors, Aryl Hydrocarbon/*agonists
MH  - Transcription, Genetic/drug effects
MH  - beta-Galactosidase/biosynthesis/genetics
EDAT- 2005/07/22 09:00
MHDA- 2005/12/13 09:00
CRDT- 2005/07/22 09:00
PHST- 2005/07/22 09:00 [pubmed]
PHST- 2005/12/13 09:00 [medline]
PHST- 2005/07/22 09:00 [entrez]
AID - kfi260 [pii]
AID - 10.1093/toxsci/kfi260 [doi]
PST - ppublish
SO  - Toxicol Sci. 2005 Oct;87(2):529-36. doi: 10.1093/toxsci/kfi260. Epub 2005 Jul 20.