Since ochratoxin A (OTA) was discovered, it has been ubiquitous as a natural contaminant of moldy food and feed. The multiple toxic effects of OTA are a real threat for human beings and animal health. For example, OTA can cause porcine nephropathy but can also damage poultries. Humans exposed to OTA can develop (notably by inhalation in the development of acute renal failure within 24 h) a range of chronic disorders such as upper urothelial carcinoma. OTA plays the main role in the pathogenesis of some renal diseases including Balkan endemic nephropathy, kidney tumors occurring in certain endemic regions of the Balkan Peninsula, and chronic interstitial nephropathy occurring in Northern African countries and likely in other parts of the world. OTA leads to DNA adduct formation, which is known for its genotoxicity and carcinogenicity. The present article discusses how renal carcinogenicity and nephrotoxicity cause both oxidative stress and direct genotoxicity. Careful analyses of the data show that OTA carcinogenic effects are due to combined direct and indirect mechanisms (e.g., genotoxicity, oxidative stress, epigenetic factors). Altogether this provides strong evidence that OTA carcinogenicity can also occur in humans.

Department Bioprocess and amp

Department of Biology Faculty of Science University of Hradec Kralove Hradec Kralove 50003 Czech Republic

Institute of State and Law Czech Academy of Sciences Narodni 18 Prague 11600 Czech Republic

Microbial Systems Laboratory Chemical Engineering INP ENSA Toulouse University of Toulouse UMR 5503 CNRS INPT UPS Auzeville Tolosane 31320 France

National Reference Center for Microfungi and Mycotoxins in Food Chains Center of Health Nutrition and Food in Brno National Institute of Public Health Prague Brno 61242 Czech Republic

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$a Malir, Frantisek $u Department of Biology, Faculty of Science, University of Hradec Kralove, Hradec Kralove 50003, Czech Republic. frantisek.malir@uhk.cz.

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$a Ochratoxin A: 50 Years of Research / $c F. Malir, V. Ostry, A. Pfohl-Leszkowicz, J. Malir, J. Toman,

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$a Since ochratoxin A (OTA) was discovered, it has been ubiquitous as a natural contaminant of moldy food and feed. The multiple toxic effects of OTA are a real threat for human beings and animal health. For example, OTA can cause porcine nephropathy but can also damage poultries. Humans exposed to OTA can develop (notably by inhalation in the development of acute renal failure within 24 h) a range of chronic disorders such as upper urothelial carcinoma. OTA plays the main role in the pathogenesis of some renal diseases including Balkan endemic nephropathy, kidney tumors occurring in certain endemic regions of the Balkan Peninsula, and chronic interstitial nephropathy occurring in Northern African countries and likely in other parts of the world. OTA leads to DNA adduct formation, which is known for its genotoxicity and carcinogenicity. The present article discusses how renal carcinogenicity and nephrotoxicity cause both oxidative stress and direct genotoxicity. Careful analyses of the data show that OTA carcinogenic effects are due to combined direct and indirect mechanisms (e.g., genotoxicity, oxidative stress, epigenetic factors). Altogether this provides strong evidence that OTA carcinogenicity can also occur in humans.

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$a Ostry, Vladimir $u National Reference Center for Microfungi and Mycotoxins in Food Chains, Center of Health, Nutrition and Food in Brno, National Institute of Public Health in Prague, Brno 61242, Czech Republic. ostry@chpr.szu.cz.

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$a Pfohl-Leszkowicz, Annie $u Department Bioprocess & Microbial Systems, Laboratory Chemical Engineering, INP/ENSA Toulouse, University of Toulouse, UMR 5503 CNRS/INPT/UPS, Auzeville-Tolosane 31320, France. leszkowicz@ensat.fr.

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$a Malir, Jan $u Institute of State and Law, Czech Academy of Sciences, Narodni 18, Prague 11600, Czech Republic. jan.malir@ilaw.cas.cz.

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$a Toman, Jakub $u Department of Biology, Faculty of Science, University of Hradec Kralove, Hradec Kralove 50003, Czech Republic. jakub.toman.1@uhk.cz.

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