Document Detail


Metabolism of dacarbazine by rat liver microsomes contribution of CYP1A enzymes to dacarbazine N-demethylation.
MedLine Citation:
PMID:  9531528     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The N-demethylation of dacarbazine in liver microsomes was significantly increased by treatment of rats with beta-naphthoflavone, dexamethasone, or phenobarbital. However, the extent of increase in the N-demethylation observed in beta-naphthoflavone-treated rats was much greater than that observed in dexamethasone-treated rats. A good correlation between N-demethylation of dacarbazine and O-deethylation of phenacetin was observed when a low concentration of phenacetin was used. Furthermore, the activity of dacarbazine N-demethylase in rat liver microsomes was highly correlated with the amounts of CYP protein immunochemically determined with anti-rat CYP1A2 antibodies. In addition, antibodies to rat CYP1A2, and furafylline and alpha-naphthoflavone, which are known inhibitors of CYP1A enzymes, exhibited inhibitory effects on dacarbazine N-demethylation. These results indicated that CYP1A enzymes may be responsible for N-demethylation of dacarbazine in rat liver microsomes.
Authors:
S Yamagata; S Ohmori; N Suzuki; M Yoshino; M Hino; I Ishii; M Kitada
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Drug metabolism and disposition: the biological fate of chemicals     Volume:  26     ISSN:  0090-9556     ISO Abbreviation:  Drug Metab. Dispos.     Publication Date:  1998 Apr 
Date Detail:
Created Date:  1998-05-14     Completed Date:  1998-05-14     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9421550     Medline TA:  Drug Metab Dispos     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  379-82     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Antineoplastic Agents / metabolism*
Cytochrome P-450 CYP1A2 / metabolism
Cytochrome P-450 Enzyme System / metabolism*
Dacarbazine / metabolism*
Male
Microsomes, Liver / metabolism*
Rats
Rats, Sprague-Dawley
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 4342-03-4/Dacarbazine; 9035-51-2/Cytochrome P-450 Enzyme System; EC 1.14.14.1/Cytochrome P-450 CYP1A2

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


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