ATLA::Alternatives to Laboratory Animals

Volume 29, Number 3

Metabolic activity in primary cultures of fish hepatocytes.

ATLA 29, 251-257, May/June 2001

Helmut Segner1 and Jean-Pierre Cravedi2

lDepartment of Chemical Ecotoxicology, Centre for Environmental Research, Permoserstrasse 15, 04318 Leipzig, Germany; 2Laboratoire des Xénobiotiques, INRA, 180 chemin de Tournefeuille, 31931 Toulouse, France

SUMMARY

In aquatic toxicology, isolated liver cells from fish can be used as a tool to generate initial information on the hepatic metabolism of xenobiotics, and on the mechanisms of xenobiotic activation or deactivation. This isolation of teleost liver cells is achieved by enzymic dissociation, and monolayer cultures of fish hepatocytes in serum-free medium maintain good viability for 3-8 days. During in vitro culture, fish liver cells express stable levels of phase I and phase II enzymes, such as cytochrome P4501A or glutathione S-transferase, and the cells show an induction of biotransformation enzymes after exposure to xenobiotics. The xenobiotic metabolite pattern produced by fish hepatocytes in vitro is generally similar to that observed in vivo. Limitations to moreintensive application of cultured fish hepatocytes as a screen in aquatic hazard assessment are partly due to the rather limited scope of existing studies, i.e. the focus on one particular species (rainbow trout), and on one particular biotransformation enzyme (cytochrome P450 1A), as well as a lack of comparative in vitro/in vivo studies.

Keywords: hepatocytes, teleost fish, biotransformation, in vitro culture, cytochrome P4501A