Skip Navigation


ToxSci Advance Access originally published online on April 15, 2003
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
73/2/315    most recent
kfg073v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (33)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Lühe, A.
Right arrow Articles by Ahr, H.-J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lühe, A.
Right arrow Articles by Ahr, H.-J.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Toxicological Sciences 73, 315-328 (2003)
Copyright © 2003 by the Society of Toxicology

GENETIC TOXICOLOGY

A New Approach to Studying Ochratoxin A (OTA)-Induced Nephrotoxicity: Expression Profiling in Vivo and in Vitro Employing cDNA Microarrays

Anke Lühe*,1, Heinz Hildebrand{dagger}, Ute Bach{ddagger}, Theodor Dingermann§ and Hans-Jürgen Ahr{dagger}

* Department of Molecular and Genetic Toxicology, {dagger} Department of Molecular and Genetic Toxicology, and {ddagger} Department of Pathology, Bayer AG, Aprather Weg 18a, 42096 Wuppertal, Germany; and § Institute of Pharmaceutical Biology, Johann Wolfgang Goethe Universität, Marie-Curie-Str. 9, 60439 Frankfurt/Main, Germany

ABSTRACT

Ochratoxin A (OTA) is a mycotoxin often found in cereals as a contaminant, and it is known to cause severe nephrotoxicity in animals and humans. There have been several investigations studying the mode of action of this toxicant, suggesting inhibition of protein synthesis, formation of DNA adducts, and provocation of DNA single-strand breaks as a result of oxidative stress, but little is known about the transcriptional alterations underlying OTA-derived nephrotoxicity so far. We carried out DNA microarray analyses to assess OTA-specific expression profiles in vivo and in vitro. Cultures of primary rat proximal tubular cells and male Wistar rats were treated with a low dose (5 µM and 1 mg/kg, respectively) or a high dose (12.5 µM and 10 mg/kg, respectively) of OTA for 24 or 72 h. Microarray experiments were carried out after dual fluorescent labeling of sample cDNA, and data analysis was performed utilizing different statistical methods. Validity of selected microarray data was confirmed by quantitative real-time PCR. We were able to demonstrate that microarray data derived from our proximal tubule cell (PTC) culture model were highly comparable to the in vivo situation. Marked treatment-specific transcriptional changes were detected for genes involved in DNA damage response and apoptosis (upregulation of GADD 153, GADD 45, annexin V), response to oxidative stress (differential expression of hypoxia-inducible factor 1 and catalase), and inflammatory reactions (upregulation of alpha 2 macroglobulin, ceruloplasmin, and cathepsin S). We conclude that our results provide a molecular basis for interpretation of OTA-induced nephrotoxicity.

Key Words: toxicogenomics; microarray; expression profiling; Ochratoxin A; nephrotoxicity; kidney; proximal tubule; cell culture.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Toxicol SciHome page
E. Rached, D. Hoffmann, K. Blumbach, K. Weber, W. Dekant, and A. Mally
Evaluation of Putative Biomarkers of Nephrotoxicity after Exposure to Ochratoxin A In Vivo and In Vitro
Toxicol. Sci., June 1, 2008; 103(2): 371 - 381.
[Abstract] [Full Text] [PDF]

Home page
 Nephrol Dial TransplantHome page
K. J. A. Vanhoutte, C. Laarakkers, E. Marchiori, P. Pickkers, J. F. M. Wetzels, J. L. Willems, L. P. van den Heuvel, F. G. M. Russel, and R. Masereeuw
Biomarker discovery with SELDI-TOF MS in human urine associated with early renal injury: evaluation with computational analytical tools
Nephrol. Dial. Transplant., October 1, 2007; 22(10): 2932 - 2943.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
E. Rached, G. C. Hard, K. Blumbach, K. Weber, R. Draheim, W. K. Lutz, S. Ozden, U. Steger, W. Dekant, and A. Mally
Ochratoxin A: 13-Week Oral Toxicity and Cell Proliferation in Male F344/N Rats
Toxicol. Sci., June 1, 2007; 97(2): 288 - 298.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
K. Stemmer, H. Ellinger-Ziegelbauer, H.-J. Ahr, and D. R. Dietrich
Carcinogen-Specific Gene Expression Profiles in Short-term Treated Eker and Wild-type Rats Indicative of Pathways Involved in Renal Tumorigenesis
Cancer Res., May 1, 2007; 67(9): 4052 - 4068.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
E. D. Kharasch, J. L. Schroeder, T. Bammler, R. Beyer, and S. Srinouanprachanh
Gene Expression Profiling of Nephrotoxicity from the Sevoflurane Degradation Product Fluoromethyl-2,2-difluoro-1-(trifluoromethyl)vinyl Ether ("Compound A") in Rats
Toxicol. Sci., April 1, 2006; 90(2): 419 - 431.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
M. Marin-Kuan, S. Nestler, C. Verguet, C. Bezencon, D. Piguet, R. Mansourian, J. Holzwarth, M. Grigorov, T. Delatour, P. Mantle, et al.
A Toxicogenomics Approach to Identify New Plausible Epigenetic Mechanisms of Ochratoxin A Carcinogenicity in Rat
Toxicol. Sci., January 1, 2006; 89(1): 120 - 134.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
B. Rohrer, F. R. Pinto, K. E. Hulse, H. R. Lohr, L. Zhang, and J. S. Almeida
Multidestructive Pathways Triggered in Photoreceptor Cell Death of the RD Mouse as Determined through Gene Expression Profiling
J. Biol. Chem., October 1, 2004; 279(40): 41903 - 41910.
[Abstract] [Full Text] [PDF]


Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.