title: Toxicity and metabolism of ochratoxin A.
abstract: The frequent occurrence of ochratoxin A (OA) in food and feed commodities and the high incidence of human exposure, as confirmed by different surveillance studies initiated several investigations devoted to elucidating the molecular mechanisms underlying OA toxicity. Previous studies indicated that the primary effects of OA are the inhibition of tRNA synthetase, the inhibition of mitochondrial respiration, and a disturbance of intracellular calcium homeostasis inherent to lipid peroxidation processes. We here report the effect of OA on a number of toxicological endpoints including cytotoxicity in different cell lines and effects on macromolecular synthesis and cell proliferation in primary cultures of hepatocytes at concentrations corresponding to overall exposure levels. These studies provide evidence that prominent toxicological effects might be linked to biotransformation processes. Analysis of hepatic biotransformation resulted in the detection of a number of distinct stable OA-metabolites. As metabolic activation has also been identified as an essential step in OA mutagenicity, the biological relevance on this mechanistic data is discussed.
authors.affiliation: Department of Veterinary Pharmacology, Pharmacy, and Toxicology, Faculty of Veterinary Medicine, Utrecht University, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Fink-Gremmels
authors.forename: A
authors.initials: A
authors.lastname: Jahn
authors.forename: M J
authors.initials: MJ
authors.lastname: Blom
mesh_terms: D000818:Animals; D001711:Biotransformation; D002273:Carcinogens / Q000633:toxicity*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D004247:DNA / Q000096:biosynthesis; D006367:HeLa Cells; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009793:Ochratoxins / Q000378:metabolism / Q000633:toxicity*; D014176:Protein Biosynthesis; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002273:Carcinogens; D009793:Ochratoxins; C025589:ochratoxin A; D004247:DNA