Document Detail

Effects of benzo(e)pyrene and benzo(a)pyrene on P-glycoprotein-mediated transport in Caco-2 cell monolayer: a comparative approach.
MedLine Citation:
PMID:  17408918     Owner:  NLM     Status:  MEDLINE    
The previous studies from our laboratory reported that benzo(a)pyrene (Bap) influenced efflux transport of rhodamine 123 (Rho-123) by induction of P-glycoprotein (P-gp) in Caco-2 cells. The present study investigated whether induction of P-gp and the enhanced efflux transport of Rho-123 were caused by benzo(e)pyrene (Bep), which has a structure similar to Bap, but is not a carcinogenic compound. In Caco-2 monolayer exposed to 50 microM Bep for 72 h, the ratio of the apparent permeability coefficient (P(app)) of Rho-123 efflux increased significantly compared to that of the control monolayer. Similarly, a significant increase in expression of MDR1 mRNA and of P-gp at the protein level were detected by RT-PCR and by Western blot analysis, respectively, in Caco-2 cells exposed to Bep, compared to that of the control. Caco-2 cells exposed to Bep showed oxidative stress that was detected by fluorescence microscopy using aminophenyl fluorescein. However, the oxidative stress was weaker compared with that of Bap. The cellular GSH content was decreased to 80% or 59% of control cells, respectively, in Caco-2 cells exposed to either Bep or Bap. Our results further show that Bep or Bap-induced P-gp in Caco-2 cells might have been the result of oxidative stress rather than DNA damage.
Narumi Sugihara; Kumiko Toyama; Tastuaki Okamoto; Masaaki Kadowaki; Kazumi Terao; Koji Furuno
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Publication Detail:
Type:  Journal Article     Date:  2007-02-24
Journal Detail:
Title:  Toxicology in vitro : an international journal published in association with BIBRA     Volume:  21     ISSN:  0887-2333     ISO Abbreviation:  Toxicol In Vitro     Publication Date:  2007 Aug 
Date Detail:
Created Date:  2007-04-25     Completed Date:  2007-09-25     Revised Date:  2009-04-10    
Medline Journal Info:
Nlm Unique ID:  8712158     Medline TA:  Toxicol In Vitro     Country:  England    
Other Details:
Languages:  eng     Pagination:  827-34     Citation Subset:  IM    
Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Sanzou, Fukuyama, Hiroshima 729-0292, Japan.
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MeSH Terms
Benzo(a)pyrene / toxicity*
Benzopyrenes / toxicity*
Biological Transport, Active / drug effects
Blotting, Western
Caco-2 Cells
Carcinogens / toxicity*
Cell Survival / drug effects
DNA Damage / drug effects
Glutathione / metabolism
Microscopy, Fluorescence
Oxidative Stress / drug effects
P-Glycoprotein / physiology*
Polycyclic Hydrocarbons, Aromatic / toxicity
RNA, Messenger / biosynthesis,  genetics
Reverse Transcriptase Polymerase Chain Reaction
Rhodamine 123
Reg. No./Substance:
0/Benzopyrenes; 0/Carcinogens; 0/P-Glycoprotein; 0/Polycyclic Hydrocarbons, Aromatic; 0/RNA, Messenger; 192-97-2/benzo(e)pyrene; 50-32-8/Benzo(a)pyrene; 62669-70-9/Rhodamine 123; 70-18-8/Glutathione

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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