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Influence of Inducers of Cytochrome P-450 on Dealkylation of 7-Alkoxycoumarins

  • D. Müller
  • Th Groh
  • F. K. Splinter
Part of the Archives of Toxicology book series (TOXICOLOGY, volume 14)

Abstract

P-450 dependent monooxygenation, which is responsible for detoxication and toxication of many xenobiotics, can be induced by many substances. Depending on the inducer, different P-450 forms are induced, which differ in their substrate specificity and in their involvement in the formation of toxic and carcinogenic metabolites. Therefore in toxicological investigations a sensitive and specific detection of the extent and type of induction is important. A simple detection is possible by measuring the metabolism of model substrates, e.g. ethylresorufin O-deethylation depends specifically on P-450 forms induced by, β-NF and other polycyclic aromatic hydrocarbons (Guengerich et al 1982), whereas pentylresorufin O-depentylation is considerably, but not specifically, induced by PB (Lubet et al 1985). Among 7-alkoxycoumarin derivatives 7-ethoxycoumarin was mostly used as a model substrate; its deethylation is induced by, β-NF and PB (Guengerich et al 1982). The aim of this study was to find 7-alkoxycoumarins and 7-alkoxy-4-methylcoumarins whose 7-dealkylation depends more specifically on certain P-450 forms.

Keywords

Polycyclic Aromatic Hydrocarbon Model Substrate Simple Detection Microsomal Cytochrome Germany Introduction 
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.

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References

  1. Guengerich FP, Dannan GA, Wright ST, Martin MV, Kaminsky LS (1982) Purification and characterization of liver microsomal cytochromes P-450: electrophoretic, spectral, catalytic, and immuno-chemical properties and inducibility of eight iso-zymes isolated from rats treated with phenobarbital or, β-naphthoflavone. Biochemistry 21:6019–6030PubMedCrossRefGoogle Scholar
  2. Lubet RA, Mayer RT, Cameron JW, Nims RW, Burke MD, Wolff TH, Guengerich FP (1985) A rapid and sensitive assay for measuring induction of cytochrome(s) P-450 by phenobarbital and other xenobiotics in the rat. Arch Biochem Biophys 238:43–48PubMedCrossRefGoogle Scholar
  3. Müller D (1990) Influence of xenobiotics on drug metabolism and its sensitive detection. Exp Pathol 39:187–194PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1991

Authors and Affiliations

  • D. Müller
    • 1
  • Th Groh
    • 1
  • F. K. Splinter
    • 1
  1. 1.Institut für Pharmakologie und ToxikologieFriedrich-Schiller-UniversitätJenaGermany

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