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Cytotechnology

, Volume 12, Issue 1–3, pp 357–366 | Cite as

Cytochromes P450 and drug resistance

  • Johannes Doehmer
  • Arnold R. Goeptar
  • Nico P. E. Vermeulen
Article

Abstract

Cytochromes P450 are the key enzymes for activating and inactivating many drugs, in particular anticancer drugs. Therefore, individual expression levels of cytochromes P450 may play a crucial role in drug safety and drug efficacy. Overexpression of cytochrome P450 may yield rapid turnover and elimination of drugs before the target site was reached and any pharmacological effect is observed. Therefore, it may be vital to know the individual cytochrome P450 status in order to select the appropriate drug before drug resistance occurs. Expression levels and activity of cytochromes P450 depend on many different factors. These factors include tissue and organ specific expression, sex- and age-dependent expression, genetic differences yielding polymorphic forms, competitive inhibition or induction of cytochromes P450 due to multiple drug interaction, nutrition and diet. Genetically engineered test cells defined for cytochromes P450 are available for studying drugs for metabolic activation and for identifying the metabolically competent cytochrome P450 isoform.

Key words

anticancer drugs cytochrome P450 drug resistance metabolic activation 

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Copyright information

© Kluwer Academic Publishers 1993

Authors and Affiliations

  • Johannes Doehmer
    • 1
  • Arnold R. Goeptar
    • 2
  • Nico P. E. Vermeulen
    • 2
  1. 1.Institut für Toxikologie und UmwelthygieneTechnische Universität MünchenMünchenGermany
  2. 2.Leiden/Amsterdam Center for Drug Research, Division of Molecular ToxicologyFree University AmsterdamAmsterdamThe Netherlands

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