Transcriptomic alterations induced by Ochratoxin A in rat and human renal proximal tubular in vitro models and comparison to a rat in vivo model

Paul Jennings, Christina Weiland, Alice Limonciel, Katarzyna M Bloch, Robert Radford, Lydia Aschauer, Tara McMorrow, Anja Wilmes, Walter Pfaller, Hans J Ahr, Craig Slattery, Edward A Lock, Michael P Ryan, Heidrun Ellinger-Ziegelbauer

Research output: Contribution to JournalArticleAcademicpeer-review


Ochratoxin A (OTA) is a widely studied compound due to its role in renal toxicity and carcinogenicity. However, there is still no consensus on the exact mechanisms of toxicity or carcinogenicity. In the current study, we analysed the effect of OTA on three human renal proximal tubular models (human primary, RPTEC/TERT1 and HK-2 cells) and two rat renal proximal tubular models (rat primary and NRK-52E cells). Global transcriptomics analysis at two exposure times was performed to generate a set of 756 OTA sensitive genes. This gene set was then compared in more detail across all models and additionally to a rat in vivo renal cortex model. The results demonstrate a well-conserved response across all models. OTA resulted in deregulation of a number of pathways including cytoskeleton, nucleosome regulation, translation, transcription, ubiquitination and cell cycle pathways. Interestingly, the oxidative stress activated Nrf2 pathway was not enriched. These results point to an epigenetic action of OTA, perhaps initiated by actin binding as the actin remodelling gene, advillin was the highest up-regulated in all models. The largest model differences were observed between the human and the rat in vitro models. However, since the human in vitro models were more similar to the rat in vivo model, it is more likely that these differences are model-specific rather than species-specific per se. This study demonstrates the usefulness of in vitro cell culture models combined with transcriptomic analysis for the investigation of mechanisms of toxicity and carcinogenicity. In addition, these results provide further evidence supporting a non-genotoxic mechanism of OTA-induced carcinogenicity.

Original languageEnglish
Pages (from-to)571-89
Number of pages19
JournalArchives of Toxicology
Issue number4
Publication statusPublished - Apr 2012


  • Animals
  • Carcinogens
  • Cell Line
  • DNA
  • Epigenesis, Genetic
  • Gene Expression
  • Gene Expression Profiling
  • Humans
  • Kidney Tubules, Proximal
  • Male
  • Mycotoxins
  • Ochratoxins
  • Rats
  • Rats, Wistar
  • Species Specificity
  • Toxicity Tests
  • Comparative Study
  • Journal Article


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