| Renal Toxicogenomic Response to Chronic Uranyl Nitrate Insult in Mice Magali Taulan,1,2 François Paquet,1 Christophe Maubert,1 Olivia Delissen,1 Jacques Demaille,2 and Marie-Catherine Romey2 1Institut de Radioprotection et de Sûreté Nucléaire, Laboratoire de Radiotoxicologie Expérimentale, Pierrelatte, France; 2Institut de Génétique Humaine, Laboratoire de Génétique Moléculaire et Chromosomique, Montpellier, France Abstract
Although the nephrotoxicity of uranium has been established through numerous animal studies, relatively little is known about the effects of long-term environmental uranium exposure. Using a combination of conventional biochemical studies and serial analysis of gene expression (SAGE) , we examined the renal responses to uranyl nitrate (UN) chronic exposure. Renal uranium levels were significantly increased 4 months after ingestion of uranium in drinking water. Creatinine levels in serum were slightly but significantly increased compared with those in controls. Although no further significant differences in other parameters were noted, substantial molecular changes were observed in toxicogenomic profiles. UN induced dramatic alterations in expression levels of more than 200 genes, mainly up-regulated, including oxidative-response-related genes, genes encoding for cellular metabolism, ribosomal proteins, signal transduction, and solute transporters. Seven differentially expressed transcripts were confirmed by real-time quantitative polymerase chain reaction. In addition, significantly increased peroxide levels support the implication of oxidative stress in UN toxicant response. This report highlights the potential of SAGE for the discovery of novel toxicant-induced gene expression alterations. Here, we present, for the first time, a comprehensive view of renal molecular events after uranium long-term exposure. Key words: drinking water, gene expression profiles, long-term exposure, mice, SAGE, toxicogenomics, uranyl nitrate. Environ Health Perspect 112:1628-1635 (2004) . doi:10.1289/txg.7296 available via http://dx.doi.org/ [Online 15 October 2004]
Address correspondence to M-C. Romey, Laboratoire de Génétique Moléculaire et Chromosomique, Institut de Génétique Humaine, 141, Route de la Cardonille, 34396 Montpellier Cedex 05, France. Telephone: 33 4 67 41 53 64. Fax: 33 4 67 41 53 65. E-mail: Marie-Catherine.Romey@igh.cnrs.fr We thank M. Claraz-Donnadieu, F. Petitot, and S. Frelon for helpful discussions. The authors declare they have no competing financial interests. Received 28 May 2004 ; accepted 14 October 2004.
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