Influence of Inducers of Cytochrome P-450 on Dealkylation of 7-Alkoxycoumarins
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.
KeywordsPolycyclic Aromatic Hydrocarbon Model Substrate Simple Detection Microsomal Cytochrome Germany Introduction
Unable to display preview. Download preview PDF.
- 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