Precision-cut rat liver slices in dynamic organ culture for structure-toxicity studies

We describe a novel in vitro mammalian liver system, which simplifies both metabolism and hepatotoxicity studies in a multitude of species. This system is based on mechanical cutting of slices with high precision and culture of such slices under dynamic organ culture conditions. This system permits study of intoxication or metabolism for many hours to days and is suitable for integrative biochemical assays as well as histological and morphological evaluation. We report the toxicity exhibited by the isomeric dichlorobenzenes, which in Sprague-Dawley rat liver slices is M>O>P. We also compared a series of bromobenzene analogs, which in Sprague-Dawley rat liver slices are toxic in the following sequence DBB > BB > BBN > BA > BBT > BT. The toxicity of medium chain length branched-chain fatty acids related to valproic acid also was evaluated in this system. Results show that toxicity increased with chain length in α-methyl fatty acids and depended on the location of the carboxyl group in branched-chain octanoic acids. These examples serve to illustrate the utility of precision-cut rat liver slices in dynamic organ culture for structure-toxicity studies.