The project has three parts, which are started simultaneously since different research groups are involved in the project.

Part 1 consists of the establishment of suitable cell models for performing toxicological studies with hepatocytes. We are going to add HepaRG cells to already existing HepG2 and HUH cell lines. In addition, we are going to characterize 3-dimensional human hepatocytes. We are also going to prepare hepatocytes containing genes enabling to detect ROS generation in different cellular compartments.

Part 2 describes the application of these systems and analytical techniques for studying diverse known hepatotoxins. The idea is to find out mechanisms of toxicity, proof these mechanisms in cellular systems, find out potential susceptibility factors and proof such factors in genetically manipulated cells and in experimental animals. If suitable, such susceptibility factors can also be tested using a large tissue biobank and/or in cohorts of patients with drug-induced induced liver injury.

In Part 3, the cellular uptake and the toxicity of nanoparticles will be tested in our established hepatocyte systems and in experimental animals.