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An update on direct genotoxicity as a molecular mechanism of ochratoxin a carcinogenicity

Pfohl-Leszkowicz, Annie and Manderville, Richard A. An update on direct genotoxicity as a molecular mechanism of ochratoxin a carcinogenicity. (2011) Chemical Research in Toxicology, 25 (2). 252-262. ISSN 0893-228X

(Document in English)

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Official URL: http://dx.doi.org/10.1021/tx200430f


Ochratoxin A (OTA) is a naturally occurring chlorophenolic fungal toxin that contaminates a wide range of food products and poses a cancer threat to humans. The mechanism of action (MOA) for OTA renal carcinogenicity is a controversial issue. In 2005, direct genotoxicity (covalent DNA adduct formation) was proposed as a MOA for OTA mediated carcinogenicity [Manderville, R. A. (2005) Chem. Res. Toxicol. 18, 1091-1097]. At that time, inconsistent results had been published on OTA genotoxicity/mutagenicity, and conclusive evidence for OTA-mediated DNA adduction had been lacking. In this update, published data from the past 6-7 years are presented that provide new hypotheses for the MOA of OTA-mediated carcinogenicity. While direct genotoxicity remains a controversial issue for OTA, new findings from the Umemura and Nohmi laboratories provide definitive results for the mutagenicity of OTA in the target tissue (outer medulla) of male rat kidney that rules out oxidative DNA damage. These findings, coupled with our own efforts that provide new structural evidence for DNA adduction by OTA, has strengthened the argument for involvement of direct genotoxicity in OTA-mediated renal carcinogenesis. This MOA should be taken into consideration for OTA human risk assessment.

Item Type:Article
HAL Id:hal-03469167
Audience (journal):International peer-reviewed journal
Uncontrolled Keywords:
Institution:French research institutions > Centre National de la Recherche Scientifique - CNRS (FRANCE)
Université de Toulouse > Institut National Polytechnique de Toulouse - Toulouse INP (FRANCE)
Université de Toulouse > Université Toulouse III - Paul Sabatier - UT3 (FRANCE)
Other partners > University of Guelph (CANADA)
Laboratory name:
Deposited On:04 Nov 2013 13:22

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