ATLA::Alternatives to Laboratory Animals

Volume 23, Number 1

Toxicity testing with hepatocytes: some methodological aspects.

ATLA 23, 91-96, January/February 1995

Jeffrey R. Fry, Alison H. Hammond, Mukadder Atmaca, Perminder Dhanjal and David J. Wilkinson

Department of Physiology and Pharmacology, University of Nottingham Medical School, Queen's Medical Centre, Nottingham NG7 2UH, UK

SUMMARY

Two conventional systems -- freshly-isolated hepatocytes and hepatocytes in culture -- are now widely used for toxicity testing, each possessing advantages and disadvantages. More-recently developed alternative strategies, which try to minimise the disadvantages apparent in the conventional systems, are described. Results obtained from these alternative strategies are presented, and the importance of culture as a determinant of toxic response is emphasised. Evidence is presented that reduction of the tetrazolium dye, MTT, is a measure of nucleotide redox balance in hepatocytes, rather than of mitochondrial performance as previously believed.

Keywords: hepatocytes, toxicity, culture age, storage, MTT reduction