DMD Celsis microsomes equal better data

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

Drug Metabolism and Disposition Fast Forward
First published on January 24, 2007; DOI: 10.1124/dmd.106.013532

0090-9556/07/3504-633-639$20.00
DMD 35:633-639, 2007

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
dmd.106.013532v1
35/4/633    most recent
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Armbrecht, H. J.
Right arrow Articles by Zenser, T. V.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Armbrecht, H. J.
Right arrow Articles by Zenser, T. V.

Metabolism of a Heterocyclic Amine Colon Carcinogen in Young and Old Rats

Harvey J. Armbrecht, Vijaya M. Lakshmi, Jason Wickstra, Fong Fu Hsu, and Terry V. Zenser

St. Louis Veterans Affairs Medical Center, St. Louis, Missouri (H.J.A.,V.M.L., J.W., T.V.Z.); Division of Geriatric Medicine (H.J.A.,V.M.L., T.V.Z.) and Department of Biochemistry and Molecular Biology (H.J.A., T.V.Z.), St. Louis University School of Medicine, St. Louis, Missouri; and Department of Medicine, Washington University School of Medicine, St. Louis, Missouri (F.F.H.)

The incidence of colon cancer increases with age, and this may be related to altered metabolism and disposition of carcinogens. One such carcinogen implicated in colon cancer is the heterocyclic amine found in well done meat, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ). The purpose of these studies was to determine whether the disposition and metabolism of IQ changes with age, comparing young (3-month) and old (22- to 24-month) male F344 rats. Animals were treated with vehicle or ß-naphthoflavone (BNF), an inducer of drug-metabolizing cytochromes P450. Disposition and metabolism of IQ were determined after i.p. injection of radiolabeled IQ. Urinary IQ metabolites were identified and quantitated by high-performance liquid chromatography and mass spectroscopy. In BNF-treated animals, total radiolabeled IQ excretion by old rats was less than half that of young rats. Binding of radiolabeled IQ metabolites by the old kidney was 10 times higher than that of the young. There were no age differences in intestinal and hepatic binding. There was a significant age-related increase in IQ conjugation to glucuronic acid and a decrease in conjugation to sulfate regardless of treatment. The induction of renal CYP1A1, a major P450 involved in IQ metabolism, by BNF did not change with age. Changes in IQ metabolism with age along with altered renal function may contribute to the decreased urinary excretion and increased renal binding of IQ and/or its metabolites seen in the old animals.

Address correspondence to: Dr. Harvey J. Armbrecht, Geriatric Center (11G-JB), St. Louis VA Medical Center, St. Louis, MO 63125. E-mail: hjarmbrec{at}aol.com




This article has been cited by other articles:


Home page
 Drug Metab. Dispos.Home page
V. M. Lakshmi, F. F. Hsu, and T. V. Zenser
N-Demethylation Is a Major Route of 2-Amino-3-Methylimidazo[4,5-f]quinoline Metabolism in Mouse
Drug Metab. Dispos., June 1, 2008; 36(6): 1143 - 1152.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2007 by the American Society for Pharmacology and Experimental Therapeutics.