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Formation of Covalent DNA Adducts by Enzymatically Activated Carcinogens and Drugs In Vitro and Their Determination by 32P-postlabeling
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Role of Cytochrome P450 Monooxygenase in Carcinogen and Chemotherapeutic Drug Metabolism

B Wahlang1, K Cameron Falkner1, Matt C Cave2

  • 1Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Louisville, Louisville, Kentucky, USA.

Advances in Pharmacology (San Diego, Calif.)
|August 3, 2015
PubMed

Insights

Human cytochromes P450 (CYPs) are crucial for metabolizing chemical carcinogens and anticancer drugs. Understanding CYP gene variations can help identify at-risk populations and optimize cancer therapies.

Area of Science:

  • Pharmacogenomics
  • Drug Metabolism
  • Biochemistry

Background:

  • Cytochromes P450 (CYPs) play a significant role in xenobiotic metabolism.
  • Previous research utilized animal models and expressed human CYPs to identify carcinogen-metabolizing enzymes.
  • Studies on butter yellow and benzo[α]pyrene elucidated CYP activity and induction.

Purpose of the Study:

  • To identify human cytochromes P450 (CYPs) involved in the metabolism of chemical carcinogens and anticancer drugs.
  • To review the metabolism of key anticancer drugs, including cyclophosphamide, procarbazine, and anthracycline antibiotics.
  • To explore the impact of human CYP gene polymorphisms on carcinogen and anticancer drug metabolism.

Main Methods:

  • Literature review of studies on animal models and expressed human CYPs.
  • Analysis of biochemical properties of CYP activity.
  • Review of human metabolism data for cyclophosphamide, procarbazine, and anthracycline antibiotics.
  • Examination of research on CYP gene polymorphisms and their effects.

Main Results:

  • Specific human CYPs involved in carcinogen metabolism have been identified.
  • Rodent CYP studies provide comparative insights.
  • Anticancer drugs like cyclophosphamide, procarbazine, and anthracyclines are extensively metabolized by CYPs.
  • Human CYP gene polymorphisms significantly influence the metabolism of foreign compounds.

Conclusions:

  • Understanding CYP involvement in drug and carcinogen metabolism is vital.
  • CYP gene variations offer insights into individual susceptibility to environmental carcinogens.
  • Pharmacogenomic data can personalize cancer therapy for improved efficacy and reduced toxicity.
Keywords:
Anthracycline antibioticsCarcinogen metabolismCyclophosphamideCytochrome P450Gene expressionGene polymorphismNuclear receptorsProcarbazineReactive chemical intermediates

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