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.
hepatocytes; primary culture; cytogenetics; cytotoxicity; genotoxicity
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