title: Opportunities and challenges in using human hepatocytes in cytochromes P450 induction assays.
abstract: BACKGROUND
  Identification of inducers of xenobiotic-metabolizing cytochromes P450 (CYP) is of topical interest. The issue mainly concerns three sectors: (i) preclinical testing of drug candidates and testing existing drugs and their combinations; (ii) food safety applications with regard to additives, contaminants, and adulterants; (iii) environmental applications, comprising detection and identification of endocrine disruptors.
  
  
  METHODS
  A literature search was performed using the PubMed database, covering state-of-the-art of human hepatocyte (HH) culture use, and their exploitation for the identification of P450 inducers. A list of CYP inducers identified by HHs is provided.
  
  
  CONCLUSIONS
  Primary cultures of HHs had long been considered as a gold standard for induction assays of xenobiotic-metabolizing enzymes. Owing to several shortcomings of HHs, alternative approaches such as immortalization of HHs, use of cell lines, generation of clonal cell lines from HHs, use of induced pluripotent stem (iPS) cells, cells from humanized animals, etc., were employed. While yielding particular advantage, overall, alternatives to HHs still remain an avenue for discrete applications or technical situations. Thus, HHs remain the most suitable model for complex CYP induction studies. The summary may be effectively expressed by strength/weakness/opportunity/threats analysis.
authors.affiliation: a Department of Cell Biology and Genetics, Faculty of Science , Palacky University Olomouc , Olomouc , Czech Republic.
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Dvorak
mesh_terms: D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D065693:Cytochrome P-450 Enzyme Inducers / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000378:metabolism*; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004347:Drug Interactions; D022781:Hepatocytes / Q000201:enzymology*; D006801:Humans; D057026:Induced Pluripotent Stem Cells; D015262:Xenobiotics / Q000378:metabolism*
chemical_list: D065693:Cytochrome P-450 Enzyme Inducers; D015262:Xenobiotics; D003577:Cytochrome P-450 Enzyme System
keywords: Drug–drug interactions; drug-metabolizing enzymes; gene induction; human hepatocytes