Evaluation of renal in vitro models used in ochratoxin research

Abstract

Ochratoxin A (OTA) induces renal carcinomas in rodents with a specific localisation in the S3 segment of proximal tubules and distinct early severe tissue alterations, which have been observed also in other species. Pronounced species- and sex-specific differences in toxicity occur and similar effects cannot be excluded in humans, however precise mechanism(s) remain elusive until today. In such cases, the use of in vitro models for mechanistic investigations can be very useful; in particular if a non-genotoxic mechanism of cancer formation is assumed which include cytotoxic effects. However, potential genotoxic mechanisms can also be investigated in vitro. A crucial issue of in vitro research is the choice of the appropriate cell model. Apparently, the cellular target of OTA is the renal proximal tubular cell; therefore cells from this tissue area are the most reasonable model. Furthermore, cells from affected species should be used and can be compared to cells of human origin. Another important parameter is whether to use primary cultures or to choose a cell line from the huge variety of cell lines available. In any case, important characteristics and quality controls need to be verified beforehand. Therefore, this review discusses the renal in vitro models that have been used for the investigation of renal ochratoxin toxicity. In particular, we discuss the choice of the models and the essential parameters making them suitable models for ochratoxin research together with exemplary results from this research. Furthermore, new promising models such as hTERT-immortalised cells and 3D-cultures are briefly discussed.