ALTEX :: Alternatives to Animal Experiments

1988, Volume 2

Use of Hepatocyte Cultures in Toxicology

Urs A. Boelsterli and Willi Suter

Abt. Klinische Pharmakologie, Medizinische Klinik, Universitaetsspital, CH- Zurich, und Sandoz AG, WSP Toxikologie, Division Pharma, CH-Basel

SUMMARY

The significance of hepatocyte cultures as an alternative to animal tests in experimental toxicology and routine safety assessment of drugs and chemicals has increased during the past years. Practical applications for cytotoxicity testing of compounds range from the analysis of specific cellular mechanisms of toxicity to the determination of species differences (including man) for a given endpoint, and the screening of structural analogs. Hepatocyte cultures have been successfully used to assess genotoxicity by demonstrating various types of DNA damage. They are also used as a metabolic system for different genotoxicity assays. Using the techniques, specific information can be obtained which may be equivalent or even superior (e.g. when using human hepatocytes) to the answers provided by in vivo experiments. However, hepatocyte cultures should only be used as a complementary method in combination with animal experiments in order to optimally predict the hepatotoxic potential of drugs and chemical in man.

Keywords: hepatocyte cultures, toxicology, genotoxicity, DNA damage, drugs, chemicals