Skip Navigation



ToxSci Advance Access published online on February 20, 2007
Toxicological Sciences, doi:10.1093/toxsci/kfm022
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow All Versions of this Article:
97/1/81    most recent
kfm022v1
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 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 arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Friry-Santini, C.
Right arrow Articles by Bars, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Friry-Santini, C.
Right arrow Articles by Bars, R.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2007. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Correlation between protein accumulation profiles and conventional toxicological findings using a model antiandrogenic compound, flutamide

Claire Friry-Santini*,{dagger}, David Rouquié*, Philippe Kennel*, Helen Tinwell*, Mohamed Benahmed{dagger} and Rémi Bars*

* Bayer CropScience, Research Toxicology, Sophia-Antipolis, France {dagger} Faculté de Médecine Lyon Sud, INSERM U407, Oullins, France

Corresponding author: Rémi Bars, Bayer CropScience, 355 rue Dostoïevski, 06903 Sophia-Antipolis, France, E-mail : remi.bars{at}bayercropscience.com, Tel: 33 (0)4 92 94 34 83, Fax : 33 (0)4 93 95 84 54

Received December 11, 2006; revision received January 26, 2007; accepted February 11, 2007


  Abstract

In conventional rodent toxicity studies the characterization of the adverse effects of a chemical relies on gravimetric, histological and hormonal measurements. 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, whose toxic effects, as measured using standard approaches, are well characterized. Male Sprague-Dawley rats were orally exposed to flutamide (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 flutamide. Several proteins involved in steroidogenesis (e.g. StAR, ApoE, Hmgcs1, Idi1), cell cycle and cancer (e.g. Ddx1, Hspd1) were modulated by flutamide 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 flutamide 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.


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
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]


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.