PMID- 11164533
OWN - NLM
STAT- MEDLINE
DCOM- 20010705
LR  - 20191104
IS  - 0166-445X (Print)
IS  - 0166-445X (Linking)
VI  - 52
IP  - 2
DP  - 2001 Apr
TI  - Induction and suppression of cytochrome P450 1A by 
      3,3',4,4',5-pentachlorobiphenyl and its relationship to oxidative stress in the 
      marine fish scup (Stenotomus chrysops).
PG  - 101-15
AB  - The planar polychlorinated biphenyl (PCB) 3,3',4,4'-tetrachlorobiphenyl (TCB) 
      causes dose-dependent induction and post-transcriptional suppression of hepatic 
      cytochrome P450 1A (CYP1A) in the marine teleost scup (Stenotomus chrysops). That 
      suppression is linked to inhibition and oxidative inactivation of CYP1A by TCB. 
      Other planar PCBs, including 3,3',4,4',5-pentachlorobiphenyl (PeCB), inactivate 
      scup CYP1A in vitro leading us to hypothesize that PeCB also will suppress CYP1A 
      in vivo. We examined induction and suppression of CYP1A by PeCB in scup, as 
      related to oxidative stress. PeCB at a low dose (0.01 mg/kg) induced hepatic 
      microsomal spectral P450 and CYP1A protein and catalytic activities 
      (ethoxyresorufin o-deethylase (EROD) and methoxyresorufin o-demethylase (MROD)) 
      over an 18 day period. A high dose (1 mg PeCB/kg) only minimally induced hepatic 
      spectral P450 and CYP1A content, and EROD and MROD rates remained at control 
      levels at all sampling times, while CYP1A mRNA expression was induced strongly 
      (up to 35-fold) at both doses. High dose PeCB had minimal effects on content of 
      P450A (a CYP3A protein), P450B (a CYP2B-like protein) and cytochrome b5 in scup 
      liver, suggesting that the suppression was specific for CYP1A. High dose PeCB 
      suppressed EROD but not CYP1A protein in the kidney but did not strongly suppress 
      either CYP1A or EROD in the heart or gill. PeCB stimulated ROS production 
      (oxidation of dihydroethidium) by liver microsomes from the low dose but not the 
      high dose fish, and the rate of PeCB-stimulated ROS production was correlated 
      with EROD activity (r(2)=0.641, P<0.0005). Oxidative stress, indicated by 
      increased levels of catalase, glutathione peroxidase, glutathione reductase and 
      superoxide dismutase activities, was stimulated in the liver by low dose but not 
      high dose PeCB. The results support a hypothesis that many PHAH can inactivate 
      teleost CYP1A in vivo, and that CYP1A is a source of ROS. However, there appears 
      to be a complex balance between the effects of PeCB on the levels of active 
      CYP1A, ROS release and oxidative stress.
FAU - Schlezinger, J J
AU  - Schlezinger JJ
AD  - Biology Department, Woods Hole Oceanographic Institution, Redfield 342, MS 32, 
      Woods Hole, MA 02543, USA.
FAU - Stegeman, J J
AU  - Stegeman JJ
LA  - eng
GR  - P42-ES07381/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Netherlands
TA  - Aquat Toxicol
JT  - Aquatic toxicology (Amsterdam, Netherlands)
JID - 8500246
RN  - 0 (Cytochrome P-450 CYP1A2 Inhibitors)
RN  - 0 (RNA, Messenger)
RN  - 0 (Reactive Oxygen Species)
RN  - 9035-51-2 (Cytochrome P-450 Enzyme System)
RN  - DFC2HB4I0K (Polychlorinated Biphenyls)
RN  - EC 1.- (Oxidoreductases)
RN  - EC 1.- (methoxyresorufin-O-demethylase)
RN  - EC 1.14.14.1 (Aryl Hydrocarbon Hydroxylases)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP1A1)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP1A2)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP2B6)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP3A)
RN  - EC 1.5.- (Oxidoreductases, N-Demethylating)
RN  - TSH69IA9XF (3,4,5,3',4'-pentachlorobiphenyl)
SB  - IM
MH  - Animals
MH  - *Aryl Hydrocarbon Hydroxylases
MH  - Cytochrome P-450 CYP1A1/*antagonists & inhibitors/*biosynthesis
MH  - Cytochrome P-450 CYP1A2/*biosynthesis
MH  - *Cytochrome P-450 CYP1A2 Inhibitors
MH  - Cytochrome P-450 CYP2B6
MH  - Cytochrome P-450 CYP3A
MH  - Cytochrome P-450 Enzyme System/metabolism
MH  - Liver/enzymology
MH  - Oxidative Stress/*drug effects
MH  - Oxidoreductases/metabolism
MH  - Oxidoreductases, N-Demethylating/metabolism
MH  - Perciformes/*metabolism
MH  - Polychlorinated Biphenyls/*pharmacology
MH  - RNA, Messenger/metabolism
MH  - Reactive Oxygen Species/metabolism
EDAT- 2001/02/13 11:00
MHDA- 2001/07/06 10:01
CRDT- 2001/02/13 11:00
PHST- 2001/02/13 11:00 [pubmed]
PHST- 2001/07/06 10:01 [medline]
PHST- 2001/02/13 11:00 [entrez]
AID - S0166-445X(00)00141-7 [pii]
AID - 10.1016/s0166-445x(00)00141-7 [doi]
PST - ppublish
SO  - Aquat Toxicol. 2001 Apr;52(2):101-15. doi: 10.1016/s0166-445x(00)00141-7.