PMID- 17686919
OWN - NLM
STAT- MEDLINE
DCOM- 20071206
LR  - 20191210
IS  - 1096-6080 (Print)
IS  - 1096-0929 (Linking)
VI  - 100
IP  - 1
DP  - 2007 Nov
TI  - Evaluation of the antiandrogenic effects of flutamide, DDE, and linuron in the 
      weanling rat assay using organ weight, histopathological, and proteomic 
      approaches.
PG  - 54-65
AB  - The Organization for Economic Cooperation and Development (OECD) is currently 
      funding the validation of the Hershberger assay as a rapid in vivo means of 
      identifying (anti-) androgens. However, as the assay measures weight changes in 
      the androgen-sensitive tissues of castrated rats, the evaluation of the 
      androgen-stimulated intact weanling as a more ethical model to use in the assay 
      has been requested. As part of the OECD validation exercise two weak 
      antiandrogens, 1,1-dichloro-2,2-bis(4 chlorophenyl)ethane (DDE) and linuron 
      (LIN), were investigated in our laboratory at several dose levels in the 
      testosterone propionate (TP)-stimulated weanling using flutamide (FM) as a 
      positive control. In addition to weight measurements (sex accessory tissues 
      [SATs], epididymides, and testes), histopathological assessment of the seminal 
      vesicles, prostate, and testes was conducted for vehicle control, TP-stimulated, 
      and TP-stimulated animals treated with FM or the top dose level of DDE or LIN. 
      The modulation of a novel prostate protein associated with apoptosis, L-amino 
      acid oxidase (LAO), was evaluated in these same treatment groups. Our gravimetric 
      data (supported by the histopathology data) indicated that the weanling assay can 
      detect SAT and epididymal weight changes induced by the antiandrogens evaluated. 
      Inconsistent and variable data were recorded for the testicular weight and 
      histopathological effects, suggesting that the testis is of little value in the 
      identification of antiandrogens using this model. Three isoforms of LAO were 
      identified, and all were regulated by TP. Modulation of LAO by the antiandrogens 
      indicated that this protein could be a biomarker for endocrine disruption in male 
      rodents.
FAU - Tinwell, Helen
AU  - Tinwell H
AD  - Department of Research Toxicology, Bayer CropScience, 06903 Sophia-Antipolis, 
      France. helen.tinwell@bayercropscience.com
FAU - Friry-Santini, Claire
AU  - Friry-Santini C
FAU - Rouquie, David
AU  - Rouquie D
FAU - Belluco, Sara
AU  - Belluco S
FAU - Elies, Laetitia
AU  - Elies L
FAU - Pallen, Catherine
AU  - Pallen C
FAU - Bars, Remi
AU  - Bars R
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Validation Study
DEP - 20070808
PL  - United States
TA  - Toxicol Sci
JT  - Toxicological sciences : an official journal of the Society of Toxicology
JID - 9805461
RN  - 0 (Androgen Antagonists)
RN  - 0 (Biomarkers, Pharmacological)
RN  - 0 (Endocrine Disruptors)
RN  - 01XP1SU59O (Linuron)
RN  - 4M7FS82U08 (Dichlorodiphenyl Dichloroethylene)
RN  - 76W6J0943E (Flutamide)
RN  - EC 1.4.3.2 (L-Amino Acid Oxidase)
RN  - WI93Z9138A (Testosterone Propionate)
SB  - IM
MH  - Adrenal Glands/drug effects
MH  - Androgen Antagonists/*toxicity
MH  - Animals
MH  - Biomarkers, Pharmacological/metabolism
MH  - Body Weight/drug effects
MH  - Dichlorodiphenyl Dichloroethylene/*toxicity
MH  - Dose-Response Relationship, Drug
MH  - Endocrine Disruptors/*toxicity
MH  - Epididymis/drug effects
MH  - Flutamide/*toxicity
MH  - Genitalia, Male/*drug effects/metabolism/pathology
MH  - Kidney/drug effects
MH  - L-Amino Acid Oxidase/metabolism
MH  - Linuron/*toxicity
MH  - Liver/drug effects
MH  - Male
MH  - Organ Size/drug effects
MH  - Prostate/drug effects
MH  - *Proteomics
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reproducibility of Results
MH  - Seminal Vesicles/drug effects
MH  - Testis/drug effects
MH  - Testosterone Propionate/pharmacology
MH  - Time Factors
MH  - Toxicity Tests/*methods
MH  - Weaning
EDAT- 2007/08/10 09:00
MHDA- 2007/12/07 09:00
CRDT- 2007/08/10 09:00
PHST- 2007/08/10 09:00 [pubmed]
PHST- 2007/12/07 09:00 [medline]
PHST- 2007/08/10 09:00 [entrez]
AID - kfm208 [pii]
AID - 10.1093/toxsci/kfm208 [doi]
PST - ppublish
SO  - Toxicol Sci. 2007 Nov;100(1):54-65. doi: 10.1093/toxsci/kfm208. Epub 2007 Aug 8.