Ochratoxin A carcinogenicity involves a complex network of epigenetic mechanisms.
Ochratoxin A (OTA) is a mycotoxin occurring in a wide range of food products. Because of the limitation of human epidemiological data, the safety significance of OTA in food has to rely on animal data, with renal toxicity and carcinogenicity being considered the pivotal effects. The elucidation of the mechanism of action would improve the use of experimental animal data for risk assessment. Direct genotoxicity versus epigenetic mechanisms appears to be a key question. In the present review, the increasingly documented epigenetic cellular effects of OTA and their potential toxicological relevance are discussed. The information available suggests that OTA is unlikely to act through a single, well-defined mechanism of action. Instead, it is proposed that a network of interacting epigenetic mechanisms, including protein synthesis inhibition, oxidative stress and the activation of specific cell signalling pathways, is responsible for OTA carcinogenicity. From a risk assessment perspective, it has to be noted that the mechanisms proposed above depend mainly upon gene expression and enzyme activation, and are, therefore, likely to be thresholded.
Marin-Kuan
Maricel
M
Nestlé Research Center, Quality and Safety, PO Box 44, Vers-chez-les-Blanc, CH-1000 Lausanne 26, Switzerland. maricel.marin-kuan@rdls.nestle.com
Cavin
Christophe
C
Delatour
Thierry
T
Schilter
Benoît
B
D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D044127:Epigenesis, Genetic; D005516:Food Microbiology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D007680:Kidney Neoplasms / Q000139:chemically induced* / Q000235:genetics; D009183:Mycotoxins / Q000633:toxicity*; D009793:Ochratoxins / Q000633:toxicity*; D018570:Risk Assessment; D043922:Toxicogenetics
D002273:Carcinogens; D009183:Mycotoxins; D009793:Ochratoxins; C025589:ochratoxin A