This project will generate data on the mechanisms of tumor induction by ochratoxin A. The obtained mechanistic data should provide a better basis for the assessment of human tumor risks due to the widespread contamination of food with ochratoxin A and thus a better justification for tolerable levels of ochratoxin A in food and should thus ensure that tolerable levels for ochratoxin A can be set which are scientifically based and justifiable if challenged by anybody or in relation to restrictions on international trade.
This project will apply novel approaches and combine both studies in vivo and in relevant in vitro models to not only investigate the occurrence and nature of damage to DNA and other macromolecules induced by ochratoxin A and its metabolites but also to generate satisfactory scientific data which should also substantially contribute to risk assessment in the most quantitative manner possible.
To elucidate mechanisms of ochratoxin A tumorigenicity, this project will quantify relevant biochemical endpoints in the toxicity and tumorigenicity of ochratoxin A. Individual activities in this project will address the mechanisms of DNA-damage induced by ochratoxin A (point mutations through adduct formation, strand-breaks or other events induced by oxidative stress).