Document Detail


Cytochrome P450 1A1 (CYP1A1) in blood lymphocytes evidence for catalytic activity and mRNA expression.
MedLine Citation:
PMID:  11459429     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Studies initiated to characterise the catalytic activity and expression of CYP1A1 in rat blood lymphocytes revealed significant activity of 7-ethoxyresorufin-O-deethylase (EROD) in rat blood lymphocytes. Pretreatment with 3-methylcholanthrene (MC) and beta-naphthoflavone (NF) resulted in significant induction in the activity of lymphocyte EROD suggesting that like the liver enzyme, EROD activity in lymphocytes is inducible and is mediated by the MC inducible isoenzymes of P450. The increase in the activity of EROD was associated with a significant increase in the apparent Vmax and affinity of the substrate towards EROD. That this increase in the activity of EROD could be primarily due to the increase in the expression of CYP1A1 isoenzymes was demonstrated by RT-PCR and western immunoblotting studies indicating an increase in the expression of CYP1A1 in blood lymphocytes after MC pretreatment. Significant inhibition in the EROD activity of MC induced lymphocyte by anti-CYP1A1/1A2 and alpha-naphthoflavone further provided evidence that the CYP1A1/1A2 isoenzymes are involved in the activity of EROD in blood lymphocytes. The data indicating similarities in the regulation of CYP1A1 in blood lymphocytes with the liver isoenzyme suggests that factors which may affect expression of CYP1A1 in liver may also affect expression in blood lymphocytes and that blood lymphocytes could be used as a surrogates for studying hepatic expression of the xenobiotic metabolising enzymes.
Authors:
A Dey; D Parmar; M Dayal; A Dhawan; P K Seth
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Life sciences     Volume:  69     ISSN:  0024-3205     ISO Abbreviation:  Life Sci.     Publication Date:  2001 Jun 
Date Detail:
Created Date:  2001-07-18     Completed Date:  2001-07-26     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0375521     Medline TA:  Life Sci     Country:  England    
Other Details:
Languages:  eng     Pagination:  383-93     Citation Subset:  IM    
Affiliation:
Industrial Toxicology Research Centre, Mahatma Gandhi Marg, Lucknow, UP, India.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies / pharmacology
Benzoflavones / pharmacology
Blotting, Western
Carcinogens / pharmacology
Catalysis
Cytochrome P-450 CYP1A1 / antagonists & inhibitors,  genetics*,  metabolism*
Enzyme Induction / drug effects
Isoenzymes / antagonists & inhibitors,  genetics,  metabolism
Lymphocytes / drug effects,  enzymology*
Male
Methylcholanthrene / pharmacology
Microsomes, Liver / enzymology
Oxazines / metabolism
RNA, Messenger / biosynthesis*
Rats
Rats, Wistar
Reverse Transcriptase Polymerase Chain Reaction
beta-Naphthoflavone / pharmacology
Chemical
Reg. No./Substance:
0/Antibodies; 0/Benzoflavones; 0/Carcinogens; 0/Isoenzymes; 0/Oxazines; 0/RNA, Messenger; 56-49-5/Methylcholanthrene; 5725-91-7/ethoxyresorufin; 604-59-1/alpha-naphthoflavone; 6051-87-2/beta-Naphthoflavone; EC 1.14.14.1/Cytochrome P-450 CYP1A1

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


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