Ochratoxin A: An overview on toxicity and carcinogenicity in animals and humans.
Ochratoxin A (OTA) is a ubiquitous mycotoxin produced by fungi of improperly stored food products. OTA is nephrotoxic and is suspected of being the main etiological agent responsible for human Balkan endemic nephropathy (BEN) and associated urinary tract tumours. Striking similarities between OTA-induced porcine nephropathy in pigs and BEN in humans are observed. International Agency for Research on Cancer (IARC) has classified OTA as a possible human carcinogen (group 2B). Currently, the mode of carcinogenic action by OTA is unknown. OTA is genotoxic following oxidative metabolism. This activity is thought to play a central role in OTA-mediated carcinogenesis and may be divided into direct (covalent DNA adduction) and indirect (oxidative DNA damage) mechanisms of action. Evidence for a direct mode of genotoxicity has been derived from the sensitive 32P-postlabelling assay. OTA facilitates guanine-specific DNA adducts in vitro and in rat and pig kidney orally dosed, one adduct comigrates with a synthetic carbon (C)-bonded C8-dG OTA adduct standard. In this paper, our current understanding of OTA toxicity and carcinogenicity are reviewed. The available evidence suggests that OTA is a genotoxic carcinogen by induction of oxidative DNA lesions coupled with direct DNA adducts via quinone formation. This mechanism of action should be used to establish acceptable intake levels of OTA from human food sources.
Pfohl-Leszkowicz
Annie
A
Laboratoire de Génie Chimique, UMR CNRS/INPT/UPS 5503, INP/ENSA Toulouse, Auzeville-Tolosane, France.
Manderville
Richard A
RA
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D002273:Carcinogens / Q000633:toxicity*; D018736:DNA Adducts / Q000032:analysis; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007107:Immune System / Q000187:drug effects; D007668:Kidney / Q000187:drug effects; D009153:Mutagens / Q000633:toxicity; D009183:Mycotoxins / Q000633:toxicity*; D009369:Neoplasms / Q000139:chemically induced; D009793:Ochratoxins / Q000032:analysis / Q000493:pharmacokinetics / Q000633:toxicity*; D014018:Tissue Distribution
D002273:Carcinogens; D018736:DNA Adducts; D009153:Mutagens; D009183:Mycotoxins; D009793:Ochratoxins; C025589:ochratoxin A