Liver cell models in in vitro toxicology.

Abstract:

:In vitro liver preparations are increasingly used for the study of hepatotoxicity of chemicals. In recent years their actual advantages and limitations have been better defined. The cell models, slices, and mainly primary hepatocyte cultures, appear to be the most powerful in vitro systems, as liver-specific functions and responsiveness to inducers are retained either for a few days or several weeks depending on culture conditions. Maintenance of phase I and phase II xenobiotic metabolizing enzyme activities allows various chemical investigations to be performed, including determination of kinetic parameters, metabolic profile, interspecies comparison, inhibition and induction effects, and drug-drug interactions. In vitro liver cell models also have various applications in toxicology: screening of cytotoxic and genotoxic compounds, evaluation of chemoprotective agents, and determination of characteristic liver lesions and associated biochemical mechanisms induced by toxic compounds. Extrapolation of the results to the in vivo situation remains a matter of debate. Presently, the most convincing applications of liver cell models are the studies on different aspects of metabolism and mechanisms of toxicity. For the future, there is a need for better culture conditions and differentiated hepatocyte cell lines to overcome the limited availability of human liver tissues. In addition, strategies for in vitro analysis of potentially toxic chemicals must be better defined.

authors

Guillouzo A

doi

10.1289/ehp.98106511

subject

Has Abstract

pub_date

1998-04-01 00:00:00

pages

511-32

eissn

0091-6765

issn

1552-9924

journal_volume

106 Suppl 2

pub_type

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