Liver cell models in in vitro toxicology

被引:303
作者
Guillouzo, A [1 ]
机构
[1] Fac Pharm, INSERM, U456, Unite Detoxicat & Reparat Tussulaire, F-35043 Rennes, France
关键词
in vitro liver models; primary cultures; in vitro toxicology; xenobiotic metabolism; human hepatocytes; animal hepatocytes; cytotoxicity; genotoxicity; screening; mechanism of toxicity;
D O I
10.2307/3433803
中图分类号
X [环境科学、安全科学];
学科分类号
08 ; 0830 ;
摘要
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.
引用
收藏
页码:511 / 532
页数:22
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