PMID- 18373956
OWN - NLM
STAT- MEDLINE
DCOM- 20080619
LR  - 20181201
IS  - 1532-0456 (Print)
IS  - 1532-0456 (Linking)
VI  - 147
IP  - 4
DP  - 2008 May
TI  - Hepatic biotransformation responses in Atlantic salmon exposed to retinoic acids 
      and 3,3',4,4'-tetrachlorobiphenyl (PCB congener 77).
PG  - 470-82
LID - 10.1016/j.cbpc.2008.02.002 [doi]
AB  - Active derivatives of vitamin A are essential in physiological processes such as 
      cell growth, differentiation, morphogenesis and development. The biological 
      functions of vitamin A are mediated through the retinoid acid receptors (RARs) 
      and retinoid X receptors (RXRs). Aryl hydrocarbon receptor (AhR) agonists such as 
      planar halogenated compounds are known to interfere with vitamin A homeostasis in 
      both field and laboratory studies. In this study, we have investigated the 
      molecular interactions between vitamin A and AhR signalling pathways using 
      juvenile Atlantic salmon and agonists for both receptor pathways. Groups of 
      juvenile salmon were treated with all-trans- and 9-cis-retinoic acid mixture (7:3 
      ratio) dissolved in DMSO (dimethyl sulfoxide) at 0.1, 1 and 10 mg/kg fish weight. 
      The mixture was force fed singly or in combination with 0.1 mg 
      3,3',4,4'-tetrachlorobiphenyl (co-planar congener 77)/kg fish weight dissolved in 
      DMSO. Liver samples were collected 3 days after PCB-77 exposure. A separate group 
      exposed to combined retinoic acid (1 mg/kg for 5 days) and PCB-77, was sampled at 
      3, 7 and 14 days after PCB-77 exposure. Liver samples collected from all exposure 
      groups were analyzed for gene (RARalpha, AhR2alpha, AhR2beta, CYP1A1, UGT1 and 
      GSTpi) expression using real-time PCR and activity (7-ethoxyresorufin 
      O-deethylase (EROD), UGT and GST) using biochemical methods with specific 
      substrates. Our data showed that exposure to RA alone did not produce a 
      significant increase of RARalpha mRNA levels, and the presence of PCB-77 
      attenuated the expression of RARalpha in RA dose- and time-specific manner. In 
      addition, RA produced a dose-dependent increase of CYP1A1 mRNA and activity 
      (EROD) levels without concomitant increase in AhR2 isoforms. When administered 
      alone, PCB-77 produced increased CYP1A1, UGT1 and GSTpi mRNA and enzyme levels. 
      The PCB-77-induced CYP1A1, UGT1 and GSTpi (mRNA and activity) levels were 
      modulated by RA, in a parameter and dose-specific manner. In general, our data 
      show an interaction between vitamin A and AhR signalling that may affect retinoid 
      homeostasis in fish.
FAU - Arukwe, Augustine
AU  - Arukwe A
AD  - Department of Biology, Norwegian University of Science and Technology (NTNU), 
      Hoyskoleringen 5, 7491 Trondheim, Norway. arukwe@bio.ntnu.no
FAU - Nordbo, Bard
AU  - Nordbo B
LA  - eng
PT  - Journal Article
DEP - 20080219
PL  - United States
TA  - Comp Biochem Physiol C Toxicol Pharmacol
JT  - Comparative biochemistry and physiology. Toxicology & pharmacology : CBP
JID - 100959500
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Retinoic Acid Receptor alpha)
RN  - 1UA8E65KDZ (Alitretinoin)
RN  - 5688UTC01R (Tretinoin)
RN  - DFC2HB4I0K (Polychlorinated Biphenyls)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP1A1)
RN  - Y2I6546TMI (3,4,3',4'-tetrachlorobiphenyl)
SB  - IM
MH  - Alitretinoin
MH  - Animals
MH  - Antineoplastic Agents/*pharmacokinetics
MH  - Biotransformation
MH  - Cytochrome P-450 CYP1A1/biosynthesis
MH  - Drug Interactions
MH  - Enzyme Induction/drug effects
MH  - Female
MH  - Gene Expression Regulation, Enzymologic/drug effects
MH  - Liver/*metabolism
MH  - Male
MH  - Microsomes, Liver/metabolism
MH  - Polychlorinated Biphenyls/*pharmacokinetics
MH  - Receptors, Retinoic Acid/genetics/metabolism
MH  - Retinoic Acid Receptor alpha
MH  - *Salmo salar
MH  - Signal Transduction
MH  - Tretinoin/*pharmacokinetics
EDAT- 2008/04/01 09:00
MHDA- 2008/06/20 09:00
CRDT- 2008/04/01 09:00
PHST- 2007/10/29 00:00 [received]
PHST- 2008/02/07 00:00 [revised]
PHST- 2008/02/09 00:00 [accepted]
PHST- 2008/04/01 09:00 [pubmed]
PHST- 2008/06/20 09:00 [medline]
PHST- 2008/04/01 09:00 [entrez]
AID - S1532-0456(08)00030-6 [pii]
AID - 10.1016/j.cbpc.2008.02.002 [doi]
PST - ppublish
SO  - Comp Biochem Physiol C Toxicol Pharmacol. 2008 May;147(4):470-82. doi: 
      10.1016/j.cbpc.2008.02.002. Epub 2008 Feb 19.