A review on ochratoxin A transcriptomic studies

• Published in: Food and chemical toxicology Vol. 59; pp. 766 - 783
• Main Authors: Vettorazzi, Ariane, van Delft, Joost, López de Cerain, Adela
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.09.2013; Elsevier
• Subjects: Animals; apoptosis; Biological and medical sciences; calcium; carcinogens; Carcinogens - toxicity; cell proliferation; cell viability; cytoskeleton; DNA damage; Gene expression; gene expression regulation; Gene Expression Regulation, Neoplastic - drug effects; genes; homeostasis; Humans; in vivo studies; Kidney - drug effects; Kidney - metabolism; Kidney Neoplasms - chemically induced; Kidney Neoplasms - metabolism; mechanism of action; Medical sciences; Microarrays; mitogen-activated protein kinase; Mycotoxin; Mycotoxins - toxicity; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Ochratoxin A; Ochratoxins - toxicity; oxidative stress; Plant poisons toxicology; protein synthesis; rats; Toxicogenomics; Toxicology; Transcriptome - drug effects; Transcriptomics; Gene expression; Transcriptomics; Microarrays; Ochratoxin A; Toxicogenomics; Mycotoxin; Toxin; Ochratoxin; DNA chip; Transcriptome; Review
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2013.05.043

•The main transcriptomic studies performed with ochratoxin A have been compiled.•Data have been discussed based on different proposed ochratoxin A modes of action.•The role of metabolism and transporters has also been reviewed.•Doses, times of exposure and experimental systems have been discussed. The mycotoxin Ochratoxin A (OTA) is a potent renal carcinogen in male rats. Transcriptomic studies on OTA (4 in vitro, 6 in vivo, 2 in vitro/in vivo) have been reviewed. The aim of 6 of them was mainly mechanistic whereas the rest had mostly predictive (1) or evaluation (5) purposes. An overall tendency towards gene expression downregulation was observed, probably as a result of protein synthesis inhibition. DNA damage response genes were not deregulated in most of the studies. Genes involved in acute renal injury, cell survival and cell proliferation were upregulated in several in vivo studies. Apoptosis genes were deregulated in vitro but less affected in vivo; activation of several MAPKs has been observed. Many genes related to oxidative stress or involved in cell-to-cell interaction pathways (Wnt) or cytoskeleton structure appeared to be deregulated either in vitro or in vivo. Regucalcin was highly downregulated in vivo and other calcium homeostasis genes were significantly deregulated in vitro. Genes related to OTA transport (OATs) and metabolism (CYPs) appeared downregulated in vivo. Overall, the mechanism of action of OTA remains unclear, however transcriptomic data have contributed to new mechanistic hypothesis generation and to in vitro–in vivo comparison.