J Appl Biomed 1:117-126, 2003 | DOI: 10.32725/jab.2003.026

The cultured primary hepatocyte and its application in toxicology

Peter M. Eckl^*, Nikolaus Bresgen

University of Salzburg, Institute of Genetics and General Biology, Hellbrunnerstr. 34, A-5020 Salzburg, Austria

The liver is the main organ involved in the metabolism of xenobiotic (foreign) compounds. The responsible enzymatic systems are the cytochromes P450 (mixed function oxidases or phase I reactions) and enzymes coupling larger water soluble groups to the substrate (phase II reactions). Especially during phase I reactions, highly reactive metabolites can be formed capable of interacting with DNA and causing mutations. On the other hand reactive xenobiotics may be detoxified. Therefore, the primary parenchymal liver cell (hepatocyte) appears to be the optimal and most reliable in vitro system for the determination of mutagenicity/genotoxicity. Since however, primary hepatocytes are proliferatively quiescent, a culture system had to be developed allowing for proliferation enabling the determination of induced changes at the chromosomal level. This paper summarizes the special features of primary hepatocytes, the findings on in vitro proliferation and the application of hepatocyte cultures for in vitro and ex vivo/in vitro toxicological testing.

Keywords: hepatocytes; primary culture; cytogenetics; cytotoxicity; genotoxicity

Received: May 30, 2003; Published: July 31, 2003  Show citation