PMID- 17344101
OWN - NLM
STAT- MEDLINE
DCOM- 20070529
LR  - 20161124
IS  - 1532-0456 (Print)
IS  - 1532-0456 (Linking)
VI  - 145
IP  - 3
DP  - 2007 Apr
TI  - Modulation of xenobiotic biotransformation system and hormonal responses in 
      Atlantic salmon (Salmo salar) after exposure to tributyltin (TBT).
PG  - 431-41
AB  - Multiple biological effects of tributyltin (TBT) on juvenile salmon have been 
      investigated. Fish were exposed for 7 days to waterborne TBT at nominal 
      concentrations of 50 and 250 microg/L dissolved in dimethyl sulfoxide (DMSO). 
      Hepatic samples were analyzed for gene expression patterns in the hormonal and 
      xenobiotic biotransformation pathways using validated real-time PCR method. 
      Immunochemical and several cytochrome P450 (CYP)-mediated enzyme activity 
      (ethoxyresorufin: EROD, benzyloxyresorufin: BROD, methoxyresorufin: MROD and 
      pentoxyresorufin: PROD) assays were analyzed. Our data show that TBT produced 
      concentration-specific decrease of estrogen receptor-alpha (ERalpha), 
      vitellogenin (Vtg), zona radiata protein (Zr-protein) and increase of estrogen 
      receptor-beta (ERbeta) and androgen receptor-beta (ARbeta) in the hormonal 
      pathway. In the xenobiotic biotransformation pathway, TBT produced apparent 
      increase and decrease at respective low and high concentration, on aryl 
      hydrocarbon receptor-alpha (AhRalpha), AhR nuclear translocator (ARNT) and AhR 
      repressor (AhRR) mRNA. The expression of CYP1A1 and GST showed a TBT 
      concentration-dependent decrease. The AhRbeta, CYP3A and uridine 
      diphosphoglucuronosyl transferase (UGT) mRNA expressions were significantly 
      induced after exposure to TBT. Immunochemical analysis of CYP3A and CYP1A1 
      protein levels confirmed the TBT effects observed at the transcriptional levels. 
      The effect of TBT on the biotransformation enzyme gene expressions partially 
      co-related but did not directly parallel enzyme activity levels for EROD, BROD, 
      MROD and PROD. In general, these findings confirm previous reports on the 
      endocrine effects of TBT, in addition to effects on hepatic CYP1A isoenzyme at 
      the transcriptional level that transcends to protein and enzymatic levels. The 
      induced expression patterns of CYP3A and UGT mRNA after TBT exposure, suggest the 
      involvement of CYP3A and UGT in TBT metabolism in fish. The effect of TBT on 
      CYP3A is proposed to represent another hormonal effect of TBT not previously 
      reported in any fish or lower vertebrate. The proposed androgenic effect is 
      supported by the observation that TBT also induced ARbeta mRNA expression in a 
      concentration-specific manner. To our knowledge, this is the first study that has 
      simultaneously studied multiple responses after exposure to TBT in fish.
FAU - Mortensen, Anne Skjetne
AU  - Mortensen AS
AD  - Department of Biology, Norwegian University of Science and Technology (NTNU), 
      Hogskoleringen 5, N-7491 Trondheim, Norway.
FAU - Arukwe, Augustine
AU  - Arukwe A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070202
PL  - United States
TA  - Comp Biochem Physiol C Toxicol Pharmacol
JT  - Comparative biochemistry and physiology. Toxicology & pharmacology : CBP
JID - 100959500
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Androgen)
RN  - 0 (Receptors, Aryl Hydrocarbon)
RN  - 0 (Receptors, Estrogen)
RN  - 0 (Trialkyltin Compounds)
RN  - 0 (Xenobiotics)
RN  - 4XDX163P3D (tributyltin)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP1A1)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP3A)
SB  - IM
MH  - Animals
MH  - Cytochrome P-450 CYP1A1/genetics
MH  - Cytochrome P-450 CYP3A/genetics
MH  - Dose-Response Relationship, Drug
MH  - RNA, Messenger/analysis
MH  - Receptors, Androgen/drug effects/genetics
MH  - Receptors, Aryl Hydrocarbon/drug effects/genetics
MH  - Receptors, Estrogen/drug effects/genetics
MH  - Salmo salar/*metabolism
MH  - Signal Transduction/drug effects
MH  - Trialkyltin Compounds/*toxicity
MH  - Xenobiotics/*metabolism
EDAT- 2007/03/09 09:00
MHDA- 2007/05/30 09:00
CRDT- 2007/03/09 09:00
PHST- 2006/11/15 00:00 [received]
PHST- 2007/01/26 00:00 [revised]
PHST- 2007/01/26 00:00 [accepted]
PHST- 2007/03/09 09:00 [pubmed]
PHST- 2007/05/30 09:00 [medline]
PHST- 2007/03/09 09:00 [entrez]
AID - S1532-0456(07)00057-9 [pii]
AID - 10.1016/j.cbpc.2007.01.013 [doi]
PST - ppublish
SO  - Comp Biochem Physiol C Toxicol Pharmacol. 2007 Apr;145(3):431-41. doi: 
      10.1016/j.cbpc.2007.01.013. Epub 2007 Feb 2.