RGD Reference Report - Correlation between protein accumulation profiles and conventional toxicological findings using a model antiandrogenic compound, flutamide. - Rat Genome Database

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

Authors: Friry-Santini, C  Rouquie, D  Kennel, P  Tinwell, H  Benahmed, M  Bars, R 
Citation: Friry-Santini C, etal., Toxicol Sci. 2007 May;97(1):81-93. Epub 2007 Feb 20.
RGD ID: 2302234
Pubmed: PMID:17311803   (View Abstract at PubMed)
DOI: DOI:10.1093/toxsci/kfm022   (Journal Full-text)

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.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
response to xenobiotic stimulus  IEP 2302234 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Hmgcs1  (3-hydroxy-3-methylglutaryl-CoA synthase 1)


Additional Information