Skip Navigation



ToxSci Advance Access published online on May 23, 2007
Toxicological Sciences, doi:10.1093/toxsci/kfm130
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow All Versions of this Article:
98/2/479    most recent
kfm130v1
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 Thiébault, C
Right arrow Articles by Gouget, B
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Thiébault, C
Right arrow Articles by Gouget, B
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

Uranium Induces Apoptosis and is Genotoxic to Normal Rat Kidney (NRK-52E) Proximal Cells

C Thiébault, M Carrière, S Milgram, A Simon, L Avoscan and B Gouget

Laboratoire Pierre Sue, CEA-CNRS UMR 9956, 91191 Gif sur Yvette, France

Corresponding author: THIEBAULT Céline, Laboratoire Pierre Sue, Bat 639, CEA Saclay, 91191 Gif sur Yvette, France, Phone: +33-1-69088986, Fax: +33-1-69086923, E-mail: celine.thiebault{at}cea.fr

Received February 1, 2007; revision received April 12, 2007; accepted May 1, 2007


  Abstract

Uranium (U) is a heavy metal used in the nuclear industry and for military applications. U compounds are toxic. Their toxicity is mediated either by their radioactivity or their chemical properties. Mammalian kidneys and bones are the main organs affected by U toxicity. Although the most characteristic response to U exposure is renal dysfunction, little information is available on the mechanisms of its toxicity at the molecular level. This report studied the genotoxicity of U. Apoptosis induction in normal rat kidney (NRK-52E) proximal cells was investigated as a function of exposure time or concentrations (0-800 µM). In parallel, DNA damage was evaluated by several methods. In order to distinguish between the intrinsic and the extrinsic pathways of apoptosis, caspases-8, -9, -10 assays were conducted and the mitochondrial membrane potential was measured. Three methods were selected for their complementarities in the detection of genetic lesions. The comet assay was used for the detection of primary lesions of DNA. {gamma}H2AX immunostaining was achieved to detect DNA double strand breaks. The micronucleus assay was used to detect chromosomic breaks or losses. DNA damage and apoptosis were observed in a concentration-dependent manner. This study demonstrated that U is genotoxic from 300 µM and induces caspase-dependent apoptosis cell death from 200 µM mainly through the intrinsic pathway in NRK-52E cells. These results suggest that the DNA damage caused by U is reversible at low concentration (200-400 µM) but becomes irreversible and leads to cell death for higher concentrations (500-800 µM).

Key Words: uranium; genotoxicity; apoptosis; DNA damage; renal cells; comet assay.


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. Berradi, J.-M. Bertho, N. Dudoignon, A. Mazur, L. Grandcolas, C. Baudelin, S. Grison, P. Voisin, P. Gourmelon, and I. Dublineau
Renal Anemia Induced by Chronic Ingestion of Depleted Uranium in Rats
Toxicol. Sci., June 1, 2008; 103(2): 397 - 408.
[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.