PMID- 12711302
OWN - NLM
STAT- MEDLINE
DCOM- 20030618
LR  - 20190612
IS  - 0006-291X (Print)
IS  - 0006-291X (Linking)
VI  - 304
IP  - 2
DP  - 2003 May 2
TI  - Induction of cytochrome P450 1A is required for circulation failure and edema by 
      2,3,7,8-tetrachlorodibenzo-p-dioxin in zebrafish.
PG  - 223-8
AB  - The mechanism of toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is 
      thought to result from changes in gene expression via the aryl hydrocarbon 
      receptor (AHR). The induction of cytochrome P450 1A (CYP1A) in various organs is 
      a cardinal effect of TCDD. However, whether CYP1A is involved in endpoints of 
      TCDD toxicity is controversial. We investigated the role of CYP1A in TCDD-induced 
      developmental toxicities using gene knock-down with morpholino antisense oligos. 
      Exposure of zebrafish embryos to TCDD, at concentrations eliciting the hallmark 
      endpoints of developmental toxicity, induced CYP1A in the heart and vascular 
      endothelium throughout the body. This induction by TCDD was markedly inhibited by 
      morpholinos to zebrafish arylhydrocarbon receptor 2 (zfAHR2-MO) and to zebrafish 
      CYP1A (zfCYP1A-MO). The zfAHR2-MO but not the zfCYP1A-MO inhibited zfCYP1A mRNA 
      expression, indicating the specificities of these morpholinos. Injection of 
      either zfAHR2-MO or zfCYP1A-MO blocked the representative signs of TCDD 
      developmental toxicity in zebrafish, pericardial edema and trunk circulation 
      failure. The morpholinos appeared do not affect normal development in 
      TCDD-untreated embryos. These results suggest a mediatory role of zfCYP1A 
      induction through zfAHR2 activation in causing circulation failure by TCDD in 
      zebrafish. This is the first molecular evidence demonstrating an essential 
      requirement for CYP1A induction in TCDD-evoked developmental toxicities in any 
      vertebrate species.
FAU - Teraoka, Hiroki
AU  - Teraoka H
AD  - Department of Toxicology, School of Veterinary Medicine, Rakuno Gakuen 
      University, Ebetsu, Japan. hteraoka@rakuno.ac.jp
FAU - Dong, Wu
AU  - Dong W
FAU - Tsujimoto, Yoshikazu
AU  - Tsujimoto Y
FAU - Iwasa, Hiroyuki
AU  - Iwasa H
FAU - Endoh, Daiji
AU  - Endoh D
FAU - Ueno, Naoto
AU  - Ueno N
FAU - Stegeman, John J
AU  - Stegeman JJ
FAU - Peterson, Richard E
AU  - Peterson RE
FAU - Hiraga, Takeo
AU  - Hiraga T
LA  - eng
GR  - P42-ES 07381/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (AHR2 protein, zebrafish)
RN  - 0 (Oligonucleotides, Antisense)
RN  - 0 (Polychlorinated Dibenzodioxins)
RN  - 0 (Receptors, Aryl Hydrocarbon)
RN  - 0 (Teratogens)
RN  - 0 (Zebrafish Proteins)
RN  - 9035-51-2 (Cytochrome P-450 Enzyme System)
SB  - IM
MH  - Animals
MH  - Blood Circulation/*drug effects
MH  - Cardiomyopathies/chemically induced/pathology
MH  - Cells, Cultured
MH  - Cytochrome P-450 Enzyme System/*biosynthesis/genetics/*physiology
MH  - Edema/chemically induced/pathology
MH  - Embryo, Nonmammalian/anatomy & histology/drug effects
MH  - Oligonucleotides, Antisense/pharmacology
MH  - Pericardium/pathology
MH  - Polychlorinated Dibenzodioxins/*toxicity
MH  - Receptors, Aryl Hydrocarbon/genetics/physiology
MH  - Teratogens/*toxicity
MH  - Zebrafish/*embryology/physiology
MH  - Zebrafish Proteins/genetics/physiology
EDAT- 2003/04/25 05:00
MHDA- 2003/06/19 05:00
CRDT- 2003/04/25 05:00
PHST- 2003/04/25 05:00 [pubmed]
PHST- 2003/06/19 05:00 [medline]
PHST- 2003/04/25 05:00 [entrez]
AID - S0006291X0300576X [pii]
AID - 10.1016/s0006-291x(03)00576-x [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2003 May 2;304(2):223-8. doi: 
      10.1016/s0006-291x(03)00576-x.