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Nitroarenes pp 318-318 | Cite as

Determination of Carcinogenic Arylamine N-Oxidation Phenotype in Humans by Analysis of Caffeine Urinary Metabolites

  • M. A. Butler
  • N. P. Lang
  • J. F. Young
  • G. Talaska
  • J. Massengill
  • C. Teitel
  • F. F. Kadlubar
Part of the Environmental Science Research book series (ESRH, volume 40)

Abstract

Epidemiological studies have shown wide variation in human urinary bladder and colo-rectal cancer incidences that may arise in part from genetic differences in susceptibility to carcinogenic arylamines. The hepatic N-oxidation of several primary arylamines, regarded as an important activation step leading to carcinogenesis, is catalyzed selectively by human liver cytochrome P-450 PA; and several studies have indicated that considerable inter-individual variability in P-450PA exists in human populations. Recently, we have shown that hepatic microsomal caffeine 3-demethylation, the initial major step in caffeine disposition in humans, is also selectively catalyzed by human P-450PA. Thus, caffeine 3-demethylation activity in humans may be used as an indirect measure of carcinogenic arylamine N-oxidation activity. In this study, we have developed a metabolic phenotyping procedure to assess caffeine-3-demethylation proficiency. A 200-μ1 urine sample, obtained between 4–5 hours after an individual has consumed 50–100 mg caffeine (as coffee or soft drink), is analyzed by an HPLC method that quantifies caffeine and its 14 metabolites. Pharmacokinetic studies indicate that a molar ratio of 1,7-dimethylxanthine/caffeine in this urine sample reflects quasi-steady state blood levels and closely approximates hepatic caffeine 3-demethylation activity.

Keywords

Urine Sample Pharmacokinetic Study HPLC Method Indirect Measure Soft Drink 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Copyright information

© Springer Science+Business Media New York 1990

Authors and Affiliations

  • M. A. Butler
    • 1
    • 2
  • N. P. Lang
    • 1
    • 2
  • J. F. Young
    • 1
    • 2
  • G. Talaska
    • 1
    • 2
  • J. Massengill
    • 1
    • 2
  • C. Teitel
    • 1
    • 2
  • F. F. Kadlubar
    • 1
    • 2
  1. 1.The National Center for Toxicological ResearchJeffersonUSA
  2. 2.The John A. McClellan Memorial Veterans HospitalLittle RockUSA

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