ToxSci Advance Access originally published online on February 20, 2007
Toxicological Sciences 2007 97(1):81-93; doi:10.1093/toxsci/kfm022
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Correlation between Protein Accumulation Profiles and Conventional Toxicological Findings Using a Model Antiandrogenic Compound, Flutamide
* Bayer CropScience, Research Toxicology, Sophia-Antipolis, France
Faculté de Médecine Lyon Sud, INSERM U407, Oullins, France
1 To whom correspondence should be addressed at Bayer CropScience, 355 rue Dostoïevski, 06903 Sophia-Antipolis, France. Fax: 33 (0)4-93-95-84-54. E-mail: remi.bars{at}bayercropscience.com.
Received December 11, 2006; accepted February 11, 2007
 |
Abstract |
|---|
In conventional rodent toxicity studies the characterization of the adverse effects of a chemical relies primarily on gravimetric, and histopathological data. The aim of this study was to evaluate if the use of two-dimensional gel electrophoresis could generate protein accumulation profiles, which were in accordance with conventional toxicological findings by investigating a model antiandrogen, flutamide (FM), whose toxic effects, as measured using standard approaches, are well characterized. Male Sprague-Dawley rats were orally exposed to FM (0, 6, 30, and 150 mg/kg/day) for 28 days. The expected inhibition of androgen-dependent tissue stimulation, increased luteinizing hormone and testosterone plasma levels, and Leydig cell hyperplasia were observed. Changes in testicular protein accumulation profiles were evaluated in rats exposed to 150 mg/kg/day FM. Several proteins involved in steroidogenesis (e.g., StAR, ApoE, Hmgcs1, Idi1), cell cycle, and cancer (e.g., Ddx1, Hspd1) were modulated by FM, and these data provided molecular evidence for the hormonal and testicular histopathology changes recorded. Changes in proteins associated with spermatogenesis were also recorded, and these are discussed within the context of the testicular phenotype observed following FM treatment (i.e., normal spermatogenesis but Leydig cell hyperplasia). Overall, our data indicate that the combination of conventional toxicology measurements with omic observations has the potential to improve our global understanding of the toxicity of a compound.
Key Words: antiandrogen; flutamide; testis; proteomics; two-dimensional gel electrophoresis.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  D. Rouquie, C. Friry-Santini, F. Schorsch, H. Tinwell, and R. Bars Standard and Molecular NOAELs for Rat Testicular Toxicity Induced by Flutamide Toxicol. Sci., May 1, 2009; 109(1): 59 - 65. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Tinwell, C. Friry-Santini, D. Rouquie, S. Belluco, L. Elies, C. Pallen, and R. Bars Evaluation of the Antiandrogenic Effects of Flutamide, DDE, and Linuron in the Weanling Rat Assay Using Organ Weight, Histopathological, and Proteomic Approaches Toxicol. Sci., November 1, 2007; 100(1): 54 - 65. [Abstract] [Full Text] [PDF]
|
|