PMID- 12657491
OWN - NLM
STAT- MEDLINE
DCOM- 20030429
LR  - 20191106
IS  - 0166-445X (Print)
IS  - 0166-445X (Linking)
VI  - 63
IP  - 2
DP  - 2003 Apr 10
TI  - Differential modulation of cytochrome P-450 1A and P-glycoprotein expression by 
      aryl hydrocarbon receptor agonists and thyroid hormone in Xenopus laevis liver 
      and intestine.
PG  - 173-86
AB  - Several defence mechanisms, such as cytochrome P450 1A (CYP1A) enzymes and 
      P-glycoprotein (Pgp), may influence the intracellular concentration and 
      consequently the toxicity of xenobiotics. The parallel expression of CYP1A and 
      Pgp has been investigated in mammals and, to a lesser extent in fish, in search 
      for evidence of co-ordinated responses to xenobiotic exposure. The aryl 
      hydrocarbon receptor (AHR) agonists are well known CYP1A inducers but some of 
      them resulted not to have a uniquely defined action on Pgp levels in mammalian 
      and fish species. To the best of our knowledge, no detailed studies have been 
      carried out so far on amphibians Xenopus laevis. For this reason, in this work, 
      the time dependent responses of the hepatic CYP1A and Pgp, to the prototypical 
      CYP1A inducers, benzo(a)pyrene (B(a)P), 3-methylcholanthrene (3MC) and 
      2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in X. laevis have been assessed at the 
      protein level and compared. The responsiveness of Xenopus intestinal Pgp to these 
      compounds has also been analysed, as the epithelial cells lining the lumen of 
      intestine represent another preferential site of Pgp expression. In addition, 
      since the thyroid hormone has been demonstrated to down regulate the mdr gene 
      during Xenopus development and in primary culture of Xenopus intestinal 
      epithelial cells, the effects of 3,3',5-triiodo-L-thyronine (T(3)) on CYP1A and 
      Pgp protein levels have been investigated in adult organisms. Western blot 
      evidenced that a single injection of B(a)P (100 mg/kg), 3MC (20 mg/kg), and TCDD 
      (3 microg/kg) elicited a statistically significant induction of hepatic CYP1A at 
      all time points considered (72, 120 and 168 h) which decreased in time. The same 
      trend of liver CYP1A induction was observed in T(3) treated Xenopus (15 
      microg/kg). Unlike CYP1A induction, the modulation of hepatic and intestinal Pgp 
      expression exhibits an heterogeneous pattern. The basal levels of hepatic and 
      intestinal Pgp were not statistically significant affected by treatments. In 
      particular, the hepatic Pgp levels seem not to be induced by TCDD and T(3) at all 
      times considered in comparison to control. For the first time the modulation of 
      CYP1A and Pgp levels by B(a)P, 3MC and in particular by TCDD and T(3) in Xenopus 
      has been demonstrated and the results herewith indicate that the two target 
      defence mechanisms respond to AHR agonists in a dissimilar way in terms of 
      proteins induction in Xenopus. Moreover, these data suggest additional 
      experiments in order to clarify the complex mechanism, which adjusts the parallel 
      expression of CYP1A and Pgp in Xenopus.
FAU - Colombo, Anita
AU  - Colombo A
AD  - Dipartimento di Scienze dell'Ambiente e del Territorio, Universita degli Studi di 
      Milano-Bicocca, P.zza della Scienza 1, 20126, Milano, Italy. 
      anita.colombo@unimib.it
FAU - Bonfanti, Patrizia
AU  - Bonfanti P
FAU - Orsi, Federica
AU  - Orsi F
FAU - Camatini, Marina
AU  - Camatini M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Aquat Toxicol
JT  - Aquatic toxicology (Amsterdam, Netherlands)
JID - 8500246
RN  - 0 (ATP Binding Cassette Transporter, Subfamily B, Member 1)
RN  - 0 (Carcinogens)
RN  - 0 (Environmental Pollutants)
RN  - 0 (Polychlorinated Dibenzodioxins)
RN  - 0 (Receptors, Aryl Hydrocarbon)
RN  - 3417WMA06D (Benzo(a)pyrene)
RN  - 56-49-5 (Methylcholanthrene)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP1A1)
SB  - IM
MH  - ATP Binding Cassette Transporter, Subfamily B, Member 1/*biosynthesis
MH  - Animals
MH  - Benzo(a)pyrene/*adverse effects
MH  - Blotting, Western
MH  - Carcinogens/*adverse effects
MH  - Cytochrome P-450 CYP1A1/*biosynthesis
MH  - Digestive System Physiological Phenomena
MH  - Environmental Pollutants/*adverse effects
MH  - Liver/physiology
MH  - Methylcholanthrene/*adverse effects
MH  - Polychlorinated Dibenzodioxins/*adverse effects
MH  - Receptors, Aryl Hydrocarbon/agonists
MH  - Xenopus laevis
EDAT- 2003/03/27 05:00
MHDA- 2003/04/30 05:00
CRDT- 2003/03/27 05:00
PHST- 2003/03/27 05:00 [pubmed]
PHST- 2003/04/30 05:00 [medline]
PHST- 2003/03/27 05:00 [entrez]
AID - S0166445X02001789 [pii]
AID - 10.1016/s0166-445x(02)00178-9 [doi]
PST - ppublish
SO  - Aquat Toxicol. 2003 Apr 10;63(2):173-86. doi: 10.1016/s0166-445x(02)00178-9.