In the process of drug development it is of high importance to test the safety of new drugs with predictive value for @entity1 @entity137 . A promising approach of @entity137 testing is based on shifts in gene expression profiling of the liver. @entity137 screening based on animal liver cells cannot be directly extrapolated to @entity1 due to species differences. The aim of this study was to evaluate precision-cut @entity1 liver slices as in vitro method for the prediction of @entity1 specific @entity137 by toxicogenomics. The liver slices contain all cell types of the liver in their natural architecture. This is important since drug-induced @entity137 often is a multi-cellular process. Previously we showed that toxicogenomic analysis of @entity35 liver slices is highly predictive for @entity35 in vivo @entity137 . In this study we investigated the levels of gene expression during incubation up to 24 h with Affymetrix microarray technology. The analysis was focused on a broad spectrum of genes related to stress and @entity137 , and on genes encoding for phase-I, -II and -III metabolizing enzymes and transporters. Observed changes in gene expression were associated with cytoskeleton remodeling, extracellular matrix and cell adhesion, but for the ADME-Tox related genes only minor changes were observed. PCA analysis showed that changes in gene expression were not associated with age, sex or source of the @entity1 livers. Slices treated with @entity1443 showed patterns of gene expression related to its @entity137 . These results indicate that precision-cut @entity1 liver slices are relatively stable during 24h of incubation and represent a valuable model for @entity1 in vitro hepatotoxicity testing despite the @entity1 inter-individual variability.

Gene expression analysis of precision-cut XXXX liver slices indicates stable expression of ADME-Tox related genes.

@entity1 :: ('9606', 'Species') :: ['humans', 'human'] @entity1443 :: ('MESH:D000082', 'Chemical') :: ['acetaminophen'] @entity137 :: ('MESH:D064420', 'Disease') :: ['toxicity', 'Toxicity'] @entity35 :: ('10116', 'Species') :: ['rat']
@entity1 :: (9606,Species) :: ['human']
