PMID- 10820144
OWN - NLM
STAT- MEDLINE
DCOM- 20000731
LR  - 20161124
IS  - 0090-9556 (Print)
IS  - 0090-9556 (Linking)
VI  - 28
IP  - 6
DP  - 2000 Jun
TI  - Dose and inducer-dependent induction of cytochrome P450 1A in endothelia of the 
      eel, including in the swimbladder rete mirabile, a model microvascular structure.
PG  - 701-8
AB  - Endothelium is a common site of cytochrome P450 1A (CYP1A) induction in 
      vertebrates, and endothelial CYP1A could affect the distribution and toxicity of 
      CYP1A substrates. We investigated CYP1A induction in organs rich in endothelium, 
      gill, heart, and a microvascular model, the swimbladder rete mirabile, in the 
      eel. Benzo[a]pyrene (BP) and 3, 3',4,4'-tetrachlorobiphenyl (TCB), radiolabeled 
      and injected intraperitoneally, showed similar distribution in eels, with 
      dose-dependent increases in concentration in heart and rete mirabile. BP [given 
      at 0.1, 1, and 10 mg/kg (0.4, 4, and 40 micromol/kg)], TCB [given at 0.1, 1, and 
      10 mg/kg (0.3, 3, 30, and 60 micromol/kg)], and beta-naphthoflavone (BNF) [given 
      at 0.1, 1, 5, 10, and 100 mg/kg (0.4, 4, 20, 40, and 400 micromol/kg)] induced 
      microsomal CYP1A and ethoxyresorufin O-deethylase in heart and rete mirabile. 
      Immunohistochemical analysis confirmed that induction of CYP1A in heart and rete 
      mirabile occurs in the endothelium. Increasing doses of each compound caused 
      increasing penetration of induction into the vascular bed of the rete, but with 
      BNF and BP induction penetrated further than with TCB. At high doses of BNF there 
      also was induction in epithelial cells adjacent to endothelium in gill and 
      kidney. CYP1A also was induced in heart and rete mirabile of eels from sites 
      heavily contaminated by aryl hydrocarbon receptor (AHR) agonists. The penetration 
      of CYP1A induction into capillaries of the rete mirabile reflects the penetration 
      of the inducer itself, consistent with the idea that endothelial CYP1A can 
      indicate the local distribution of AHR agonists. The microvascular rete mirabile 
      in the eel provides a model system to explore further a hypothesis that 
      endothelial CYP1A participates in removal of some AHR agonists from the 
      circulation and to examine the consequences of CYP1A induction to the vascular 
      system.
FAU - Schlezinger, J J
AU  - Schlezinger JJ
AD  - Biology Department, Woods Hole Oceanographic Institution, Woods Hole, 
      Massachusetts, 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  - United States
TA  - Drug Metab Dispos
JT  - Drug metabolism and disposition: the biological fate of chemicals
JID - 9421550
RN  - 0 (Receptors, Aryl Hydrocarbon)
RN  - 3417WMA06D (Benzo(a)pyrene)
RN  - DFC2HB4I0K (Polychlorinated Biphenyls)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP1A1)
RN  - Y2I6546TMI (3,4,3',4'-tetrachlorobiphenyl)
SB  - IM
MH  - Animals
MH  - Benzo(a)pyrene/pharmacology
MH  - Cytochrome P-450 CYP1A1/*biosynthesis
MH  - Dose-Response Relationship, Drug
MH  - Eels
MH  - Endothelium, Vascular/enzymology/*metabolism
MH  - Enzyme Induction
MH  - Gills/*enzymology/metabolism
MH  - Heart/physiology
MH  - Immunohistochemistry
MH  - Microcirculation/drug effects
MH  - Microsomes/*enzymology/metabolism
MH  - Polychlorinated Biphenyls/pharmacology
MH  - Receptors, Aryl Hydrocarbon/agonists
EDAT- 2000/05/23 09:00
MHDA- 2000/08/06 11:00
CRDT- 2000/05/23 09:00
PHST- 2000/05/23 09:00 [pubmed]
PHST- 2000/08/06 11:00 [medline]
PHST- 2000/05/23 09:00 [entrez]
PST - ppublish
SO  - Drug Metab Dispos. 2000 Jun;28(6):701-8.