title: Ochratoxin A carcinogenicity involves a complex network of epigenetic mechanisms.
abstract: 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.
authors.affiliation: Nestlé Research Center, Quality and Safety, PO Box 44, Vers-chez-les-Blanc, CH-1000 Lausanne 26, Switzerland. maricel.marin-kuan@rdls.nestle.com
authors.forename: Maricel
authors.initials: M
authors.lastname: Marin-Kuan
authors.forename: Christophe
authors.initials: C
authors.lastname: Cavin
authors.forename: Thierry
authors.initials: T
authors.lastname: Delatour
authors.forename: Benoît
authors.initials: B
authors.lastname: Schilter
mesh_terms: 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
chemical_list: D002273:Carcinogens; D009183:Mycotoxins; D009793:Ochratoxins; C025589:ochratoxin A