Ochratoxin A is a mycotoxin which contaminates a variety of human food. In experimental animals, ochratoxin A is nephrotoxic and induces tumours, in the kidney, but also in other organs of rodents. In humans, exposure to high levels of ochratoxin A in diet has been linked with chronic renal disease (Balkan endemic nephropathy, interstitial nephritis) and an increased incidence of urinary tract tumours.
The objective is to elucidate mechanisms of ochratoxin A tumorigenicity, this project intends to quantify relevant biochemical endpoints in the toxicity and tumorigenicity of ochratoxin A. Individual projects will address the mechanisms of DNA-damage induced by ochratoxin A and the time course of ochratoxin A induced changes on the biochemical, cellular and morphological level during tumorigenesis. In addition to providing information on mechanisms of tumour induction by ochratoxin A, the project will also give relevant information on mechanisms of tumour induction, promotion and progression in the kidney. The major focus is to obtain information on the dose-response curve for ochratoxin A-induced toxic effects and the relevance of observations made in animals at high dose for human risk assessment.
In the 1st year, methods for quantification of ochratoxin A induced effects will be evaluated, in the 2nd year samples will be generated and analysed in the 3rd year. An improved understanding of mechanisms resulting in DNA-damage by ochratoxin A and their role in tumorigenesis will be obtained. In addition, relevant information on tumour induction and progression in the kidney will be available after completion of the project.