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(log ppb) HPRT VF (x 10

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Metabolism Studies:<br />

Liver in vitro metabolism systems<br />

Model<br />

Isolated perfused<br />

liver<br />

Liver slices<br />

Hepatocytes<br />

Liver cell lines<br />

Subcellular fractions<br />

Genetically<br />

engineered cells<br />

Liver in vitro metabolism systems<br />

Characteristics<br />

Ex vivo organ culture; complete liver enzymes and cofactors; bile flow<br />

Closest to in vivo<br />

Ex vivo tissue culture; complete liver enzymes and cofactors; cell-cell<br />

interactions, cryopreservation limited - Close to in vivo,<br />

Ex vivo cell culture; from livers or biopsies; complete liver enzymes<br />

and cofactors; cryopreservation possible – Cell culture<br />

In vitro cell culture; variable enzyme spectra; enzyme activities<br />

limited; genotype instability; cryopreservation possible – Cell Culture<br />

Protein suspension; ER-bound and cytosolic enzymes; lack of<br />

cofactors; cryopreservation possible – enzyme preparation<br />

In vitro cell culture or protein suspension; Enzymes produced in ER<br />

of host cells (bacteria, yeast, mammalian cell lines or baculovirus);<br />

with or without cofactors – arteficial system<br />

Modified according to Guillouzo A (1998) Environmental Health Perspectives <strong>10</strong>6(2), 511-532. and Coecke S et al. (2006) ATLA 34, 49-84.

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